Is ABCC1 p.Met476Val (c.1426A>G) pathogenic?

ABCC1 p.Met476Val (c.1426A>G) is classified Uncertain significance in ABCC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-21). AlphaMissense: likely benign (0.2042); Very rare (popmax 0.00134%, afr).

How common is ABCC1 p.Met476Val (c.1426A>G) in the general population?

ABCC1 p.Met476Val (c.1426A>G) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about ABCC1 p.Met476Val (c.1426A>G)?

AlphaMissense predicts likely benign (score 0.2042) — an in-silico prediction, not a clinical call.

ABCC1 p.Met476Val

c.1426A>G · rs1276682146 · VCV3127034

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2042 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2042	likely benign
REVEL	0.513	indeterminate
SaProt	LLR -8.86	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.1	GERP -0.41, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 97 kb · p 2.5e-06 · regional, not allelic
Overall
CADD	23.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,828 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000558% 9/1,613,804 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,828
European (non-Finnish)	0.000678%	147,497

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: ABCC1
Protein: p.Met476Val
Coding: c.1426A>G
MANE Select: NM_004996
dbSNP: rs1276682146
Type: single nucleotide variant
Location: chr16:16052769 (GRCh38)
Gene constraint: LOEUF 0.564 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.01 · 5 PDB
Residue 476: the abc transmembrane type-1 1 domain

Full ABCC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCC1 p.Thr1464Met Uncertain significance ★★ ⚠ same type
ABCC1 c.1381-5C>G Benign ★★ same type
ABCC1 p.Ala1260= Benign ★★ same type
ABCC1 p.Ala1406= Benign ★★ same type
ABCC1 p.Arg433Ser Benign ★★ same type
ABCC1 p.Asp637= Likely benign ★★ same type
ABCC1 p.Gly762= Benign/Likely benign ★★ same type
ABCC1 p.Gly885= 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/abcc1-p-met476val (accessed [today's date]).

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