Is ABCC6 p.Ala950Thr (c.2848G>A) pathogenic?

ABCC6 p.Ala950Thr (c.2848G>A) is classified Conflicting classifications of pathogenicity in ABCC6 (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2025-12-26). AlphaMissense: likely benign (0.0676); Ultra-rare (popmax 0.017%, mid); Associated with arterial calcification, generalized, of infancy, 2.

What condition is associated with ABCC6 p.Ala950Thr (c.2848G>A)?

ABCC6 p.Ala950Thr (c.2848G>A) is associated with arterial calcification, generalized, of infancy, 2, pseudoxanthoma elasticum, forme fruste, autosomal recessive inherited pseudoxanthoma elasticum (ClinVar).

How common is ABCC6 p.Ala950Thr (c.2848G>A) in the general population?

ABCC6 p.Ala950Thr (c.2848G>A) is ultra-rare (popmax 0.017%, mid) (gnomAD).

How is Generalized arterial calcification of infancy inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about ABCC6 p.Ala950Thr (c.2848G>A)?

AlphaMissense predicts likely benign (score 0.0676) — an in-silico prediction, not a clinical call.

ABCC6 p.Ala950Thr

c.2848G>A · rs72657689 · VCV381637

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.0676 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.017%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

arterial calcification, generalized, of infancy, 2

Computational evidence

Protein change
AlphaMissense	0.0676	likely benign
REVEL	0.534	indeterminate
SaProt	LLR -3.87	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	Δ0.24	acceptor gain · deltas
Constraint at this position
Conservation	phyloP -2.1	GERP -3
Regional constraint	o/e 0.98	unconstrained · MANE · 59 kb · p 0.39 · regional, not allelic
Overall
CADD	13.24	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.017% Middle Eastern · 1/5,868 alleles

Filtering AF 0.00731% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00526%

Overall 0.0301% 475/1,579,638 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	1.12%	89
Remaining individualsnot grpmax-eligible	0.098%	1,020
Middle Easterngrpmax	0.017%	5,868
Admixed American	0.0147%	6,787
European (non-Finnish)	0.00679%	14,723
East Asian	0.00233%	42,968
African / African-American	0.00135%	74,260
South Asian	0.00115%	86,814

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ABCC6
Protein: p.Ala950Thr
Coding: c.2848G>A
MANE Select: NM_001171
dbSNP: rs72657689
Type: single nucleotide variant
Location: chr16:16169793 (GRCh38)
Gene constraint: LOEUF 0.917 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.32 · 4 PDB
Residue 950: a UniProt-annotated variant site (in pxe); the abc transmembrane type-1 2 domain

Full ABCC6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

arterial calcification, generalized, of infancy, 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: pseudoxanthoma elasticum, forme fruste autosomal recessive inherited pseudoxanthoma elasticum

For Generalized arterial calcification of infancy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Antenatal, Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Worldwide)

Similar variants

ABCC6 p.Ala950Val Likely benign ★★ same residue
ABCC6 c.1868-5T>G Pathogenic/Likely pathogenic ★★ same condition
ABCC6 c.2591-1G>T Likely pathogenic ★★ same condition
ABCC6 c.2787+1G>T Pathogenic ★★ same condition
ABCC6 c.3507-1G>A Pathogenic ★★ same condition
ABCC6 c.37-1G>A Pathogenic ★★ same condition
ABCC6 c.3736-1G>A Pathogenic ★★ same condition
ABCC6 c.3883-6G>A Pathogenic/Likely pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/abcc6-p-ala950thr (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown