Is BEX1 p.Ala35Val (c.104C>T) pathogenic?

BEX1 p.Ala35Val (c.104C>T) is classified Conflicting classifications of pathogenicity in BEX1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-04-02). AlphaMissense: likely benign (0.0968); Rare (popmax 0.184%, mid).

How common is BEX1 p.Ala35Val (c.104C>T) in the general population?

BEX1 p.Ala35Val (c.104C>T) is rare (popmax 0.184%, mid) (gnomAD).

What do computational predictors say about BEX1 p.Ala35Val (c.104C>T)?

AlphaMissense predicts likely benign (score 0.0968) — an in-silico prediction, not a clinical call.

BEX1 p.Ala35Val

c.104C>T · rs140998909 · VCV2454286

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0968 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.184%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0968	likely benign
REVEL	0.123	moderately benign-leaning
SaProt	LLR -6.02	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 -8.4	GERP -2.5
Regional constraint	o/e 1.13	unconstrained · MANE · 237 bp · p 0.29 · regional, not allelic
Overall
CADD	16.1	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 0.184% Middle Eastern · 8/4,352 alleles

Filtering AF 0.0914% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0667%

Overall 0.0423% 512/1,209,789 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.184%	544
Remaining individualsnot grpmax-eligible	0.0777%	1,287
European (non-Finnish)	0.0486%	2,058
South Asian	0.0317%	3,152
Finnishnot grpmax-eligible	0.0129%	7,767
Admixed American	0.00875%	11,435
African / African-American	0.007%	14,284

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: BEX1
Protein: p.Ala35Val
Coding: c.104C>T
MANE Select: NM_018476
dbSNP: rs140998909
Type: single nucleotide variant
Location: chrX:103063171 (GRCh38)
Structure: AlphaFold pLDDT 68.10

Full BEX1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BEX1 p.Ala17Asp Uncertain significance ★ ⚠ same type
BEX1 p.Arg106Trp Uncertain significance ★ ⚠ same type
BEX1 p.Arg50His Uncertain significance ★ ⚠ same type
BEX1 p.Arg54Cys Uncertain significance ★ ⚠ same type
BEX1 p.Arg54His Uncertain significance ★ ⚠ same type
BEX1 p.Arg84Lys Uncertain significance ★ ⚠ same type
BEX1 p.Asn10Asp Uncertain significance ★ ⚠ same type
BEX1 p.Asn16Asp 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/bex1-p-ala35val (accessed [today's date]).

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