Is ABCG4 p.Val164Phe (c.490G>T) pathogenic?

ABCG4 p.Val164Phe (c.490G>T) is classified Uncertain significance in ABCG4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-11). AlphaMissense: ambiguous (0.4943); Very rare (popmax 0.00144%, nfe).

How common is ABCG4 p.Val164Phe (c.490G>T) in the general population?

ABCG4 p.Val164Phe (c.490G>T) is very rare (popmax 0.00144%, nfe) (gnomAD).

What do computational predictors say about ABCG4 p.Val164Phe (c.490G>T)?

AlphaMissense predicts ambiguous (score 0.4943) — an in-silico prediction, not a clinical call.

ABCG4 p.Val164Phe

c.490G>T · VCV3413428

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4943 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00144%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4943	ambiguous
REVEL	0.456	indeterminate
SaProt	LLR -7.81	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.30	loss · gain 0.01 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 10	GERP 0.94, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 11 kb · p 4.6e-16 · regional, not allelic
Overall
CADD	32.0	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 0.00144% European (non-Finnish) · 17/1,180,014 alleles

Filtering AF 0.000878% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000717%

Overall 0.00105% 17/1,614,014 alleles · very rare

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.Val164Phe
Coding: c.490G>T
MANE Select: NM_022169
Type: single nucleotide variant
Location: chr11:119154525 (GRCh38)
Gene constraint: LOEUF 0.694 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.69
Residue 164: the abc transporter domain

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-val164phe (accessed [today's date]).

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