Is ABCC6 p.Arg1064Trp (c.3190C>T) pathogenic?

ABCC6 p.Arg1064Trp (c.3190C>T) is classified Benign/Likely benign in ABCC6 (ClinVar, Multiple submitters, 17 submitters; last evaluated 2026-06-01). AlphaMissense: likely benign (0.1518); Low-frequency (popmax 3.11%, sas); Associated with autosomal recessive inherited pseudoxanthoma elasticum.

What condition is associated with ABCC6 p.Arg1064Trp (c.3190C>T)?

ABCC6 p.Arg1064Trp (c.3190C>T) is associated with autosomal recessive inherited pseudoxanthoma elasticum, pseudoxanthoma elasticum, forme fruste, arterial calcification, generalized, of infancy, 2 (ClinVar).

How common is ABCC6 p.Arg1064Trp (c.3190C>T) in the general population?

ABCC6 p.Arg1064Trp (c.3190C>T) is low-frequency (popmax 3.11%, sas) (gnomAD).

How is Pseudoxanthoma elasticum inherited?

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

What do computational predictors say about ABCC6 p.Arg1064Trp (c.3190C>T)?

AlphaMissense predicts likely benign (score 0.1518) — an in-silico prediction, not a clinical call.

ABCC6 p.Arg1064Trp

c.3190C>T · rs41278174 · VCV433305

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 17 submitters

AlphaMissense

likely benign

0.1518 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.11%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autosomal recessive inherited pseudoxanthoma elasticum

Computational evidence

Protein change
AlphaMissense	0.1518	likely benign
REVEL	0.66	pathogenic-leaning
SaProt	LLR -8.45	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP -2, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 59 kb · p 0.39 · regional, not allelic
Overall
CADD	25.4	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 3.11% South Asian · 2,836/91,086 alleles

Filtering AF 3.02% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.98%

Overall 2.41% 38,949/1,613,760 alleles · low-frequency

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	3.44%	29
South Asiangrpmax	3.11%	32
European (non-Finnish)	2.61%	38
Remaining individualsnot grpmax-eligible	2.38%	42
Ashkenazi Jewishnot grpmax-eligible	2.12%	47
Amishnot grpmax-eligible	1.86%	54
Middle Eastern	1.75%	57
Admixed American	0.918%	109
African / African-American	0.39%	256
East Asian	0.0156%	6,411

Finnish 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.Arg1064Trp
Coding: c.3190C>T
MANE Select: NM_001171
dbSNP: rs41278174
Type: single nucleotide variant
Location: chr16:16165739 (GRCh38)
Gene constraint: LOEUF 0.917 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.32 · 4 PDB
Residue 1064: a UniProt-annotated variant site (in); the abc transmembrane type-1 2 domain

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

Disease context

autosomal recessive inherited pseudoxanthoma elasticum — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: pseudoxanthoma elasticum, forme fruste arterial calcification, generalized, of infancy, 2

For Pseudoxanthoma elasticum (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

ABCC6 p.Arg1064Gln Uncertain significance ★★ ⚠ 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-arg1064trp (accessed [today's date]).

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