Is ABR p.Ser710Arg (c.2130T>A) pathogenic?

ABR p.Ser710Arg (c.2130T>A) is classified Uncertain significance in ABR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-27). AlphaMissense: likely pathogenic (0.7591); Very rare (popmax 0.000424%, nfe).

How common is ABR p.Ser710Arg (c.2130T>A) in the general population?

ABR p.Ser710Arg (c.2130T>A) is very rare (popmax 0.000424%, nfe) (gnomAD).

What do computational predictors say about ABR p.Ser710Arg (c.2130T>A)?

AlphaMissense predicts likely pathogenic (score 0.7591) — an in-silico prediction, not a clinical call.

ABR p.Ser710Arg

c.2130T>A · VCV4180874

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7591 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7591	likely pathogenic
REVEL	0.266	benign-leaning
SaProt	LLR -11.19	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.9	GERP -3.7
Regional constraint	o/e 0.62	unconstrained · MANE · 6,609 bp · p 9.1e-11 · regional, not allelic
Overall
CADD	9.257	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 0.000424% European (non-Finnish) · 5/1,179,988 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000342% 5/1,461,598 alleles · very rare

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.Ser710Arg
Coding: c.2130T>A
MANE Select: NM_021962
Type: single nucleotide variant
Location: chr17:1010835 (GRCh38)
Gene constraint: LOEUF 0.431 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 79.10
Residue 710: 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-ser710arg (accessed [today's date]).

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