Is GABRE p.Ser102Ala (c.304T>G) pathogenic?

GABRE p.Ser102Ala (c.304T>G) is classified Benign in GABRE (ClinVar, Multiple submitters, 2 submitters; last evaluated 2020-09-14). AlphaMissense: likely benign (0.0821); Common (popmax 89.1%, eas) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about GABRE p.Ser102Ala (c.304T>G)?

AlphaMissense predicts likely benign (score 0.0821) — an in-silico prediction, not a clinical call.

GABRE p.Ser102Ala

Q: How common is GABRE p.Ser102Ala (c.304T>G) in the general population?

GABRE p.Ser102Ala (c.304T>G) is common (popmax 89.1%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.304T>G · rs1139916 · VCV1280403

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0821 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 89.1%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0821	likely benign
REVEL	0.211	benign-leaning
SaProt	LLR -5.20	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 2.3	GERP 3.4, phastCons 0.99
Regional constraint	o/e 1.02	unconstrained · MANE · 20 kb · p 0.65 · regional, not allelic
Overall
CADD	13.69	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 89.1% East Asian · 29,946/33,612 alleles

Filtering AF 88.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 87.9%

Overall 69.1% 833,708/1,206,120 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	89.1%	1
South Asian	81.7%	1
Finnishnot grpmax-eligible	79.7%	1
Admixed American	73.3%	1
Middle Eastern	70.6%	1
European (non-Finnish)	68.3%	1
Remaining individualsnot grpmax-eligible	68.3%	1
Amishnot grpmax-eligible	62.3%	2
Ashkenazi Jewishnot grpmax-eligible	61%	2
African / African-American	49.2%	2

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.Ser102Ala
Coding: c.304T>G
MANE Select: NM_004961
dbSNP: rs1139916
Type: single nucleotide variant
Location: chrX:151969707 (GRCh38)
Structure: AlphaFold pLDDT 73.13
Residue 102: a UniProt-annotated variant site (in)

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.Ala193Gly Uncertain significance ★ ⚠ same type
GABRE p.Ala193Thr Uncertain significance ★ ⚠ same type
GABRE p.Ala193Val 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-ser102ala (accessed [today's date]).

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