Is ABCG4 p.Thr511Ile (c.1532C>T) pathogenic?

ABCG4 p.Thr511Ile (c.1532C>T) is classified Uncertain significance in ABCG4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-05). AlphaMissense: likely benign (0.1585); Ultra-rare (popmax 0.0306%, afr).

How common is ABCG4 p.Thr511Ile (c.1532C>T) in the general population?

ABCG4 p.Thr511Ile (c.1532C>T) is ultra-rare (popmax 0.0306%, afr) (gnomAD).

What do computational predictors say about ABCG4 p.Thr511Ile (c.1532C>T)?

AlphaMissense predicts likely benign (score 0.1585) — an in-silico prediction, not a clinical call.

ABCG4 p.Thr511Ile

c.1532C>T · rs542544848 · VCV3129681

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1585 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0306%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1585	likely benign
REVEL	0.126	moderately benign-leaning
SaProt	LLR -6.52	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 1.4	GERP 1.2, phastCons 0.82
Regional constraint	o/e 0.72	unconstrained · MANE · 11 kb · p 4.6e-16 · regional, not allelic
Overall
CADD	16.51	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 0.0306% African / African-American · 23/75,054 alleles

Filtering AF 0.0209% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0177%

Overall 0.00254% 41/1,613,732 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0306%	3,263
Admixed American	0.0167%	6,002
Remaining individualsnot grpmax-eligible	0.0096%	10,415
East Asian	0.00446%	22,424

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.Thr511Ile
Coding: c.1532C>T
MANE Select: NM_022169
dbSNP: rs542544848
Type: single nucleotide variant
Location: chr11:119160321 (GRCh38)
Gene constraint: LOEUF 0.694 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.69
Residue 511: the abc transmembrane type-2 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-thr511ile (accessed [today's date]).

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