Is ABCC6 p.Val1202Met (c.3604G>A) pathogenic?

ABCC6 p.Val1202Met (c.3604G>A) is classified Uncertain significance in ABCC6 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-08-26). AlphaMissense: ambiguous (0.4101); Ultra-rare (popmax 0.0165%, mid); Associated with Inborn genetic diseases.

What condition is associated with ABCC6 p.Val1202Met (c.3604G>A)?

ABCC6 p.Val1202Met (c.3604G>A) is associated with Inborn genetic diseases, pseudoxanthoma elasticum, forme fruste, autosomal recessive inherited pseudoxanthoma elasticum (ClinVar).

How common is ABCC6 p.Val1202Met (c.3604G>A) in the general population?

ABCC6 p.Val1202Met (c.3604G>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about ABCC6 p.Val1202Met (c.3604G>A)?

AlphaMissense predicts ambiguous (score 0.4101) — an in-silico prediction, not a clinical call.

ABCC6 p.Val1202Met

c.3604G>A · rs752683023 · VCV1441881

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

ambiguous

0.4101 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4101	ambiguous
REVEL	0.771	pathogenic-leaning
SaProt	LLR -11.52	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	Δ0.47	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 5.8	GERP 1.7, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 59 kb · p 0.39 · regional, not allelic
Overall
CADD	34.0	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 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.00751% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00593%

Overall 0.00198% 32/1,613,928 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
South Asian	0.0132%	7,590
Remaining individualsnot grpmax-eligible	0.008%	12,500
African / African-American	0.00266%	37,524
East Asian	0.00223%	44,870
Admixed American	0.00167%	60,016
European (non-Finnish)	0.000847%	118,003

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.Val1202Met
Coding: c.3604G>A
MANE Select: NM_001171
dbSNP: rs752683023
Type: single nucleotide variant
Location: chr16:16161467 (GRCh38)
Gene constraint: LOEUF 0.917 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.32 · 4 PDB
Residue 1202: the abc transmembrane type-1 2 domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

Similar variants

ABCC6 p.Val1202= Conflicting classifications of pathogenicity ★ same residue
ABCC6 p.Val1202Leu 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

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-val1202met (accessed [today's date]).

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