Is ABR p.Arg665Gln (c.1994G>A) pathogenic?

ABR p.Arg665Gln (c.1994G>A) is classified Uncertain significance in ABR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-26). AlphaMissense: likely benign (0.1752); Ultra-rare (popmax 0.0165%, mid).

How common is ABR p.Arg665Gln (c.1994G>A) in the general population?

ABR p.Arg665Gln (c.1994G>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about ABR p.Arg665Gln (c.1994G>A)?

AlphaMissense predicts likely benign (score 0.1752) — an in-silico prediction, not a clinical call.

ABR p.Arg665Gln

c.1994G>A · VCV4636440

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1752 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1752	likely benign
REVEL	0.269	benign-leaning
SaProt	LLR -9.55	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.35 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.7	GERP 2, phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 6,609 bp · p 9.1e-11 · regional, not allelic
Overall
CADD	33.0	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 0.0165% Middle Eastern · 1/6,060 alleles

Filtering AF 0.0013% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00108%

Overall 0.0018% 29/1,613,728 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,060
East Asian	0.00446%	22,421
South Asian	0.0022%	45,531
European (non-Finnish)	0.00195%	51,293
Finnishnot grpmax-eligible	0.00156%	63,976

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: ABR
Protein: p.Arg665Gln
Coding: c.1994G>A
MANE Select: NM_021962
Type: single nucleotide variant
Location: chr17:1011953 (GRCh38)
Gene constraint: LOEUF 0.431 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 79.10
Residue 665: the rho-gap domain

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

Similar variants

ABR c.2490+4C>T Benign ★★ same type
ABR p.Ala31Glu Benign ★★ same type
ABR p.Arg124Gln Benign ★★ same type
ABR p.Glu73Asp Benign ★★ same type
ABR p.Gly114Glu Benign ★★ same type
ABR p.Gly66= Benign ★★ same type
ABR p.Ala62Thr Uncertain significance ★ ⚠ same type
ABR p.Ala688Thr 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/abr-p-arg665gln (accessed [today's date]).

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