Is ABR p.Arg657His (c.1970G>A) pathogenic?

ABR p.Arg657His (c.1970G>A) is classified Uncertain significance in ABR (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-08). AlphaMissense: likely benign (0.1296); Very rare (popmax 0.00879%, sas).

How common is ABR p.Arg657His (c.1970G>A) in the general population?

ABR p.Arg657His (c.1970G>A) is very rare (popmax 0.00879%, sas) (gnomAD).

What do computational predictors say about ABR p.Arg657His (c.1970G>A)?

AlphaMissense predicts likely benign (score 0.1296) — an in-silico prediction, not a clinical call.

ABR p.Arg657His

c.1970G>A · VCV3440178

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1296 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00879%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1296	likely benign
REVEL	0.317	indeterminate
SaProt	LLR -10.91	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
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

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00879% South Asian · 8/91,048 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00312%

Overall 0.00391% 63/1,613,184 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00879%	11,381
Remaining individualsnot grpmax-eligible	0.0048%	20,815
European (non-Finnish)	0.00398%	25,095
Finnishnot grpmax-eligible	0.00313%	31,947
East Asian	0.00223%	44,848
Admixed American	0.00167%	59,976
African / African-American	0.00133%	74,924

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.Arg657His
Coding: c.1970G>A
MANE Select: NM_021962
Type: single nucleotide variant
Location: chr17:1011977 (GRCh38)
Gene constraint: LOEUF 0.431 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 79.10
Residue 657: 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-arg657his (accessed [today's date]).

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