Is BRAP p.Val312Ala (c.935T>C) pathogenic?

BRAP p.Val312Ala (c.935T>C) is classified Uncertain significance in BRAP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-27). AlphaMissense: ambiguous (0.3705); Very rare (popmax 0.00111%, sas).

How common is BRAP p.Val312Ala (c.935T>C) in the general population?

BRAP p.Val312Ala (c.935T>C) is very rare (popmax 0.00111%, sas) (gnomAD).

What do computational predictors say about BRAP p.Val312Ala (c.935T>C)?

AlphaMissense predicts ambiguous (score 0.3705) — an in-silico prediction, not a clinical call.

BRAP p.Val312Ala

c.935T>C · rs2542166018 · VCV2489490

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3705 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00111%, sas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3705	ambiguous
REVEL	0.277	benign-leaning
SaProt	LLR -9.74	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.4, phastCons 1
Regional constraint	o/e 0.42	unconstrained · MANE · 6,923 bp · p 4.4e-13 · regional, not allelic
Overall
CADD	26.5	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 0.00111% South Asian · 1/90,178 alleles

Overall 6.87e-05% 1/1,455,778 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: BRAP
Protein: p.Val312Ala
Coding: c.935T>C
MANE Select: NM_006768
dbSNP: rs2542166018
Type: single nucleotide variant
Location: chr12:111660637 (GRCh38)
Gene constraint: LOEUF 0.766 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.92

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

Similar variants

BRAP p.Ala42= Benign ★★ same type
BRAP p.Gly250= Benign ★★ same type
BRAP p.Ile193= Benign ★★ same type
BRAP p.Lys451= Benign ★★ same type
BRAP p.Ala100Val Uncertain significance ★ ⚠ same type
BRAP p.Ala379Val Uncertain significance ★ ⚠ same type
BRAP p.Ala403Ser Uncertain significance ★ ⚠ same type
BRAP p.Ala481Gly 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/brap-p-val312ala (accessed [today's date]).

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