Is ABCC6 p.Cys203Arg (c.607T>C) pathogenic?

ABCC6 p.Cys203Arg (c.607T>C) is classified Conflicting classifications of pathogenicity in ABCC6 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-09-19). AlphaMissense: likely pathogenic (0.5739); Rare (popmax 0.167%, eas); Associated with Inborn genetic diseases.

What condition is associated with ABCC6 p.Cys203Arg (c.607T>C)?

ABCC6 p.Cys203Arg (c.607T>C) is associated with Inborn genetic diseases (ClinVar).

How common is ABCC6 p.Cys203Arg (c.607T>C) in the general population?

ABCC6 p.Cys203Arg (c.607T>C) is rare (popmax 0.167%, eas) (gnomAD).

What do computational predictors say about ABCC6 p.Cys203Arg (c.607T>C)?

AlphaMissense predicts likely pathogenic (score 0.5739) — an in-silico prediction, not a clinical call.

ABCC6 p.Cys203Arg

c.607T>C · rs556731532 · VCV2342684

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.5739 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.167%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5739	likely pathogenic
REVEL	0.72	pathogenic-leaning
SaProt	LLR -13.51	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 0.9, phastCons 1
Regional constraint	o/e 0.57	unconstrained · MANE · 5,632 bp · p 7.1e-05 · regional, not allelic
Overall
CADD	24.2	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 0.167% East Asian · 67/40,208 alleles

Filtering AF 0.135% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.123%

Overall 0.00871% 76/872,912 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.167%	600
South Asian	0.00814%	12,281
Remaining individualsnot grpmax-eligible	0.00526%	18,996
European (non-Finnish)	0.000192%	520,603

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.Cys203Arg
Coding: c.607T>C
MANE Select: NM_001171
dbSNP: rs556731532
Type: single nucleotide variant
Location: chr16:16212240 (GRCh38)
Gene constraint: LOEUF 0.917 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.32 · 4 PDB

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

Similar variants

ABCC6 p.Ala1008Val Uncertain significance ★★ ⚠ same condition
ABCC6 p.Ala101Gly Uncertain significance ★★ ⚠ same condition
ABCC6 p.Ala1370Thr Uncertain significance ★★ ⚠ same condition
ABCC6 p.Ala1385Val Uncertain significance ★★ ⚠ same condition
ABCC6 p.Ala263Gly Uncertain significance ★★ ⚠ same condition
ABCC6 p.Ala353Thr Uncertain significance ★★ ⚠ same condition
ABCC6 p.Ala488Thr Uncertain significance ★★ ⚠ same condition
ABCC6 p.Ala524Ser Uncertain significance ★★ ⚠ 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-cys203arg (accessed [today's date]).

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