Is GABRE p.Arg34His (c.101G>A) pathogenic?

GABRE p.Arg34His (c.101G>A) is classified Likely benign in GABRE (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-22). AlphaMissense: likely benign (0.0697); Very rare (popmax 0.00436%, amr).

How common is GABRE p.Arg34His (c.101G>A) in the general population?

GABRE p.Arg34His (c.101G>A) is very rare (popmax 0.00436%, amr) (gnomAD).

What do computational predictors say about GABRE p.Arg34His (c.101G>A)?

AlphaMissense predicts likely benign (score 0.0697) — an in-silico prediction, not a clinical call.

GABRE p.Arg34His

c.101G>A · VCV3518204

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0697 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00436%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0697	likely benign
REVEL	0.067	moderately benign-leaning
SaProt	LLR -6.81	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.30 · evaluated, not missing
Constraint at this position
Conservation	phyloP -3.4	GERP -7.5
Regional constraint	o/e 1.02	unconstrained · MANE · 20 kb · p 0.65 · regional, not allelic
Overall
CADD	0.016	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 0.00436% Admixed American · 2/45,868 alleles

Filtering AF 0.000723% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000482%

Overall 0.00124% 15/1,209,586 alleles · very rare exomes 14/1,097,424 · genomes 1/112,162 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00436%	22,934
Remaining individualsnot grpmax-eligible	0.00421%	23,780
European (non-Finnish)	0.00123%	81,369

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: GABRE
Protein: p.Arg34His
Coding: c.101G>A
MANE Select: NM_004961
Type: single nucleotide variant
Location: chrX:151970358 (GRCh38)
Structure: AlphaFold pLDDT 73.13
Residue 34: the 'disordered' region

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

Similar variants

GABRE p.Arg176His Uncertain significance ★★ ⚠ same type
GABRE p.Asn134= Likely benign ★★ same type
GABRE p.Glu435Asp Benign ★★ same type
GABRE p.Gly62= Benign ★★ same type
GABRE p.Leu323= Benign ★★ same type
GABRE p.Ser102Ala Benign ★★ same type
GABRE p.Ala193Gly Uncertain significance ★ ⚠ same type
GABRE p.Ala193Thr 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/gabre-p-arg34his (accessed [today's date]).

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