Is ABCG4 p.Ala5Val (c.14C>T) pathogenic?

ABCG4 p.Ala5Val (c.14C>T) is classified Uncertain significance in ABCG4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-07). AlphaMissense: likely benign (0.1243); Very rare (popmax 0.00212%, nfe).

How common is ABCG4 p.Ala5Val (c.14C>T) in the general population?

ABCG4 p.Ala5Val (c.14C>T) is very rare (popmax 0.00212%, nfe) (gnomAD).

What do computational predictors say about ABCG4 p.Ala5Val (c.14C>T)?

AlphaMissense predicts likely benign (score 0.1243) — an in-silico prediction, not a clinical call.

ABCG4 p.Ala5Val

c.14C>T · rs556090631 · VCV2460931

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1243 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00212%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1243	likely benign
REVEL	0.029	moderately benign-leaning
SaProt	LLR -7.01	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 5.9	GERP 1.8, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 11 kb · p 4.6e-16 · regional, not allelic
Overall
CADD	24.3	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 0.00212% European (non-Finnish) · 25/1,179,656 alleles

Filtering AF 0.00145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00123%

Overall 0.00192% 28/1,454,742 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00212%	47,186
Finnishnot grpmax-eligible	0.00172%	58,028
Remaining individualsnot grpmax-eligible	0.0016%	62,374
African / African-American	0.00133%	74,982

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: ABCG4
Protein: p.Ala5Val
Coding: c.14C>T
MANE Select: NM_022169
dbSNP: rs556090631
Type: single nucleotide variant
Location: chr11:119149979 (GRCh38)
Gene constraint: LOEUF 0.694 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.69

Full ABCG4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCG4 p.Asn345= Benign ★★ same type
ABCG4 p.Lys178= Benign ★★ same type
ABCG4 p.Pro352Leu Benign ★★ same type
ABCG4 p.Ala17Pro Uncertain significance ★ ⚠ same type
ABCG4 p.Ala19Thr Uncertain significance ★ ⚠ same type
ABCG4 p.Ala19Val Uncertain significance ★ ⚠ same type
ABCG4 p.Ala212Thr Uncertain significance ★ ⚠ same type
ABCG4 p.Ala234Ser Uncertain significance ★ ⚠ 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/abcg4-p-ala5val (accessed [today's date]).

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