Is ABCA2 p.Arg265Gln (c.794G>A) pathogenic?

ABCA2 p.Arg265Gln (c.794G>A) is classified Conflicting classifications of pathogenicity in ABCA2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-11-13). AlphaMissense: likely benign (0.0917); Ultra-rare (popmax 0.011%, sas); Associated with intellectual developmental disorder with poor growth and with or without seizures or ataxia.

How common is ABCA2 p.Arg265Gln (c.794G>A) in the general population?

ABCA2 p.Arg265Gln (c.794G>A) is ultra-rare (popmax 0.011%, sas) (gnomAD).

What do computational predictors say about ABCA2 p.Arg265Gln (c.794G>A)?

AlphaMissense predicts likely benign (score 0.0917) — an in-silico prediction, not a clinical call.

ABCA2 p.Arg265Gln

Q: What condition is associated with ABCA2 p.Arg265Gln (c.794G>A)?

ABCA2 p.Arg265Gln (c.794G>A) is associated with intellectual developmental disorder with poor growth and with or without seizures or ataxia (ClinVar).

c.794G>A · rs763614356 · VCV2438711

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0917 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.011%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

intellectual developmental disorder with poor growth and with or without seizures or ataxia

Computational evidence

Protein change
AlphaMissense	0.0917	likely benign
REVEL	0.236	benign-leaning
SaProt	LLR -7.07	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 -1.9	GERP -2.3
Regional constraint	o/e 1.07	unconstrained · MANE · 2,023 bp · p 0.16 · regional, not allelic
Overall
CADD	12.47	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R264Q vs ClinVar R265Q) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.011% South Asian · 10/90,666 alleles

Filtering AF 0.00596% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00455%

Overall 0.00106% 17/1,610,166 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.011%	9,067
Remaining individualsnot grpmax-eligible	0.00321%	31,171
African / African-American	0.00134%	74,856
European (non-Finnish)	0.000339%	294,727

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: ABCA2
Protein: p.Arg265Gln
Coding: c.794G>A
MANE Select: NM_001606
dbSNP: rs763614356
Type: single nucleotide variant
Location: chr9:137021495 (GRCh38)
Gene constraint: LOEUF 0.436 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.46

Full ABCA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

intellectual developmental disorder with poor growth and with or without seizures or ataxia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ABCA2 p.Gln1370Ter Likely pathogenic ★★ same condition
ABCA2 p.Ala367Thr Uncertain significance ★★ ⚠ same condition
ABCA2 p.Arg114Gln Uncertain significance ★★ ⚠ same condition
ABCA2 p.Arg1160His Uncertain significance ★★ ⚠ same condition
ABCA2 p.Arg1383His Uncertain significance ★★ ⚠ same condition
ABCA2 p.Arg1664Trp Uncertain significance ★★ ⚠ same condition
ABCA2 p.Arg954His Uncertain significance ★★ ⚠ same condition
ABCA2 p.Asn1755Lys Uncertain significance ★★ ⚠ 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/abca2-p-arg265gln (accessed [today's date]).

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