Is ABCG1 p.Arg370Trp (c.1108C>T) pathogenic?

ABCG1 p.Arg370Trp (c.1108C>T) is classified Uncertain significance in ABCG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-21). AlphaMissense: likely benign (0.1322); Ultra-rare (popmax 0.0156%, eas).

How common is ABCG1 p.Arg370Trp (c.1108C>T) in the general population?

ABCG1 p.Arg370Trp (c.1108C>T) is ultra-rare (popmax 0.0156%, eas) (gnomAD).

What do computational predictors say about ABCG1 p.Arg370Trp (c.1108C>T)?

AlphaMissense predicts likely benign (score 0.1322) — an in-silico prediction, not a clinical call.

ABCG1 p.Arg370Trp

c.1108C>T · rs757151743 · VCV2598312

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1322 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1322	likely benign
REVEL	0.494	indeterminate
SaProt	LLR -8.37	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 1.5, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 71 kb · p 0.012 · regional, not allelic
Overall
CADD	28.7	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 0.0156% East Asian · 7/44,782 alleles

Filtering AF 0.00727% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00515%

Overall 0.00261% 42/1,610,834 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0156%	6,397
Remaining individualsnot grpmax-eligible	0.00802%	12,474
South Asian	0.00551%	18,134
Admixed American	0.00504%	19,842
European (non-Finnish)	0.00187%	53,553

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: ABCG1
Protein: p.Arg370Trp
Coding: c.1108C>T
MANE Select: NM_016818
dbSNP: rs757151743
Type: single nucleotide variant
Location: chr21:42288023 (GRCh38)
Gene constraint: LOEUF 0.573 · pLI 0.20 (gnomAD)
Structure: AlphaFold pLDDT 81.34 · 5 PDB

Full ABCG1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCG1 p.Arg370Gln Uncertain significance ★ ⚠ same residue
ABCG1 p.Ala456= Benign ★★ same type
ABCG1 p.Leu643= Likely benign ★★ same type
ABCG1 p.Pro149= Benign ★★ same type
ABCG1 p.Ser547= Benign ★★ same type
ABCG1 c.1122+21A>C Uncertain significance ★ ⚠ same type
ABCG1 c.1122+24G>C Uncertain significance ★ ⚠ same type
ABCG1 c.1122+2T>C 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/abcg1-p-arg370trp (accessed [today's date]).

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