Is ABCC4 p.Val381Ile (c.1141G>A) pathogenic?

ABCC4 p.Val381Ile (c.1141G>A) is classified Likely benign in ABCC4 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-09-10). AlphaMissense: likely benign (0.0837); Rare (popmax 0.18%, nfe).

How common is ABCC4 p.Val381Ile (c.1141G>A) in the general population?

ABCC4 p.Val381Ile (c.1141G>A) is rare (popmax 0.18%, nfe) (gnomAD).

What do computational predictors say about ABCC4 p.Val381Ile (c.1141G>A)?

AlphaMissense predicts likely benign (score 0.0837) — an in-silico prediction, not a clinical call.

ABCC4 p.Val381Ile

c.1141G>A · VCV3357176

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0837 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.18%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0837	likely benign
REVEL	0.213	benign-leaning
SaProt	LLR -8.92	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.88	GERP -0.55
Regional constraint	o/e 0.59	unconstrained · MANE · 1,333 bp · p 1.8e-06 · regional, not allelic
Overall
CADD	9.275	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 0.18% European (non-Finnish) · 2,126/1,179,784 alleles

Filtering AF 0.174% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.171%

Overall 0.148% 2,381/1,613,894 alleles · rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.277%	361
European (non-Finnish)grpmax	0.18%	555
Ashkenazi Jewishnot grpmax-eligible	0.152%	658
African / African-American	0.0333%	3,001
Middle Eastern	0.033%	3,030
Admixed American	0.00833%	12,004
South Asian	0.00439%	22,770
Finnishnot grpmax-eligible	0.00156%	64,026

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val381Ile
Coding: c.1141G>A
MANE Select: NM_005845
Type: single nucleotide variant
Location: chr13:95206552 (GRCh38)
Gene constraint: LOEUF 0.647 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.42 · 25 PDB
Residue 381: an α-helix

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

Similar variants

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
ABCC4 p.Ala700= 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-val381ile (accessed [today's date]).

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