Is ABCA12 p.Arg44Gln (c.131G>A) pathogenic?

ABCA12 p.Arg44Gln (c.131G>A) is classified Uncertain significance in ABCA12 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-21). AlphaMissense: likely pathogenic (0.889); Ultra-rare (popmax 0.0286%, sas).

How common is ABCA12 p.Arg44Gln (c.131G>A) in the general population?

ABCA12 p.Arg44Gln (c.131G>A) is ultra-rare (popmax 0.0286%, sas) (gnomAD).

What do computational predictors say about ABCA12 p.Arg44Gln (c.131G>A)?

AlphaMissense predicts likely pathogenic (score 0.889) — an in-silico prediction, not a clinical call.

ABCA12 p.Arg44Gln

c.131G>A · VCV3366691

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.889 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0286%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.889	likely pathogenic
REVEL	0.693	pathogenic-leaning
SaProt	LLR -5.17	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.3, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 94 kb · p 0.48 · regional, not allelic
Overall
CADD	26.3	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 0.0286% South Asian · 26/90,990 alleles

Filtering AF 0.0199% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0171%

Overall 0.0026% 42/1,613,016 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0286%	3,500
East Asian	0.0067%	14,917
Admixed American	0.00334%	29,980
Remaining individualsnot grpmax-eligible	0.0032%	31,216
European (non-Finnish)	0.000763%	131,062

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: ABCA12
Protein: p.Arg44Gln
Coding: c.131G>A
MANE Select: NM_173076
Type: single nucleotide variant
Location: chr2:215111629 (GRCh38)
Gene constraint: LOEUF 0.582 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.32

Full ABCA12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCA12 p.Arg44Trp Likely pathogenic ★★ same residue
ABCA12 c.2592+1G>A Likely pathogenic ★★ same type
ABCA12 c.5381+1G>C Pathogenic/Likely pathogenic ★★ same type
ABCA12 c.985+1G>A Likely pathogenic ★★ same type
ABCA12 p.Arg1297Ter Pathogenic ★★ same type
ABCA12 p.Arg1514Cys Pathogenic ★★ same type
ABCA12 p.Arg1514His Pathogenic/Likely pathogenic ★★ same type
ABCA12 p.Arg1515Ter Pathogenic ★★ 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/abca12-p-arg44gln (accessed [today's date]).

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