Is ABCG1 p.Gly331= (c.993C>T) pathogenic?

ABCG1 p.Gly331= (c.993C>T) is classified Benign in ABCG1 (ClinVar, No assertion criteria, 2 submitters; last evaluated 2019-10-28). Low-frequency (popmax 3.53%, nfe); Associated with ABCG1-related disorder.

What condition is associated with ABCG1 p.Gly331= (c.993C>T)?

ABCG1 p.Gly331= (c.993C>T) is associated with ABCG1-related disorder (ClinVar).

How common is ABCG1 p.Gly331= (c.993C>T) in the general population?

ABCG1 p.Gly331= (c.993C>T) is low-frequency (popmax 3.53%, nfe) (gnomAD).

ABCG1 p.Gly331=

c.993C>T · rs56140811 · VCV3037791

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.53%, nfe)

Conditions

ABCG1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.44	donor gain · deltas
Constraint at this position
Conservation	phyloP -4.2	GERP -3.5
Overall
CADD	14.09	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.53% European (non-Finnish) · 41,212/1,169,080 alleles

Filtering AF 3.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.48%

Overall 3% 47,929/1,596,190 alleles · low-frequency

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	4.07%	25
European (non-Finnish)grpmax	3.53%	28
Remaining individualsnot grpmax-eligible	2.74%	36
Amishnot grpmax-eligible	2.74%	36
Ashkenazi Jewishnot grpmax-eligible	1.25%	80
South Asian	1.15%	87
Admixed American	1.02%	99
Middle Eastern	0.752%	133
African / African-American	0.521%	192
East Asian	0.0045%	22,237

Finnish 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: ABCG1
Protein: p.Gly331=
Coding: c.993C>T
MANE Select: NM_016818
dbSNP: rs56140811
Type: single nucleotide variant
Location: chr21:42287908 (GRCh38)
Gene constraint: LOEUF 0.573 · pLI 0.20 (gnomAD)
Structure: AlphaFold pLDDT 81.34 · 5 PDB
Residue 331: a turn

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

Disease context

ABCG1-related disorder

Similar variants

ABCG1 p.Phe640Leu Uncertain significance ⚠ same condition
ABCG1 c.538-6C>T Benign same condition
ABCG1 p.Ala203= Likely benign same condition
ABCG1 p.Asp614= Likely benign same condition
ABCG1 p.Cys3= Benign same condition
ABCG1 p.Gly358Arg Benign same condition
ABCG1 p.Leu113= Benign same condition
ABCG1 p.Phe448= Likely benign same condition

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-gly331 (accessed [today's date]).

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