Is ABCC4 p.Arg951Cys (c.2851C>T) pathogenic?

ABCC4 p.Arg951Cys (c.2851C>T) is classified Uncertain significance in ABCC4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-12). AlphaMissense: ambiguous (0.3716); Very rare (popmax 0.0011%, sas).

How common is ABCC4 p.Arg951Cys (c.2851C>T) in the general population?

ABCC4 p.Arg951Cys (c.2851C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about ABCC4 p.Arg951Cys (c.2851C>T)?

AlphaMissense predicts ambiguous (score 0.3716) — an in-silico prediction, not a clinical call.

ABCC4 p.Arg951Cys

c.2851C>T · rs1039728112 · VCV2611398

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3716 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3716	ambiguous
REVEL	0.651	pathogenic-leaning
SaProt	LLR -8.05	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.32 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.3	GERP 2, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 185 kb · p 0.00034 · regional, not allelic
Overall
CADD	26.8	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 0.0011% South Asian · 1/90,966 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000342% 5/1,461,554 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	90,966
European (non-Finnish)	0.000339%	294,983

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: ABCC4
Protein: p.Arg951Cys
Coding: c.2851C>T
MANE Select: NM_005845
dbSNP: rs1039728112
Type: single nucleotide variant
Location: chr13:95074280 (GRCh38)
Gene constraint: LOEUF 0.647 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.42 · 25 PDB
Residue 951: an α-helix; the abc transmembrane type-1 2 domain

Full ABCC4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCC4 p.Arg951His Uncertain significance ★ ⚠ same residue
ABCC4 p.Ala1282Thr Uncertain significance ★★ ⚠ same type
ABCC4 p.Ala1324Thr Uncertain significance ★★ ⚠ same type
ABCC4 p.Leu238Phe Uncertain significance ★★ ⚠ same type
ABCC4 p.Tyr788Cys Uncertain significance ★★ ⚠ same type
ABCC4 c.1825-7A>G Benign ★★ same type
ABCC4 c.185+7C>T Benign ★★ same type
ABCC4 c.307-10C>T Benign/Likely benign ★★ same type

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/abcc4-p-arg951cys (accessed [today's date]).

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