Is ABCC1 p.Val676Met (c.2026G>A) pathogenic?

ABCC1 p.Val676Met (c.2026G>A) is classified Uncertain significance in ABCC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-15). AlphaMissense: ambiguous (0.5304); Very rare (popmax 0.00533%, afr).

How common is ABCC1 p.Val676Met (c.2026G>A) in the general population?

ABCC1 p.Val676Met (c.2026G>A) is very rare (popmax 0.00533%, afr) (gnomAD).

What do computational predictors say about ABCC1 p.Val676Met (c.2026G>A)?

AlphaMissense predicts ambiguous (score 0.5304) — an in-silico prediction, not a clinical call.

ABCC1 p.Val676Met

c.2026G>A · VCV4111828

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5304 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00533%, afr)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5304	ambiguous
REVEL	0.852	moderately pathogenic-leaning
SaProt	LLR -10.90	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 0.77, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 97 kb · p 2.5e-06 · regional, not allelic
Overall
CADD	28.6	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 0.00533% African / African-American · 4/75,034 alleles

Filtering AF 0.00174% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00112% 18/1,613,896 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00533%	18,758
East Asian	0.00223%	44,874
South Asian	0.0022%	45,535
European (non-Finnish)	0.000932%	107,257

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.Val676Met
Coding: c.2026G>A
MANE Select: NM_004996
Type: single nucleotide variant
Location: chr16:16079389 (GRCh38)
Gene constraint: LOEUF 0.564 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.01 · 5 PDB
Residue 676: a β-strand; the abc transporter 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-val676met (accessed [today's date]).

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