Is BRIX1 p.Asp95Tyr (c.283G>T) pathogenic?

BRIX1 p.Asp95Tyr (c.283G>T) is classified Uncertain significance in BRIX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-22). AlphaMissense: likely pathogenic (0.966); Very rare (popmax 0.00259%, eas).

How common is BRIX1 p.Asp95Tyr (c.283G>T) in the general population?

BRIX1 p.Asp95Tyr (c.283G>T) is very rare (popmax 0.00259%, eas) (gnomAD).

What do computational predictors say about BRIX1 p.Asp95Tyr (c.283G>T)?

AlphaMissense predicts likely pathogenic (score 0.966) — an in-silico prediction, not a clinical call.

BRIX1 p.Asp95Tyr

c.283G>T · rs865965960 · VCV2487499

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.966 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00259%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.966	likely pathogenic
REVEL	0.568	indeterminate
SaProt	LLR -15.40	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.23	loss · gain 0.01 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 9,753 bp · p 0.54 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00259% East Asian · 1/38,610 alleles

Filtering AF 4.2e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.6e-05%

Overall 0.000351% 4/1,138,852 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00259%	38,610
Admixed American	0.00248%	40,386
European (non-Finnish)	0.00025%	399,345

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: BRIX1
Protein: p.Asp95Tyr
Coding: c.283G>T
MANE Select: NM_018321
dbSNP: rs865965960
Type: single nucleotide variant
Location: chr5:34919851 (GRCh38)
Gene constraint: LOEUF 0.626 · pLI 0.80 (gnomAD)
Structure: AlphaFold pLDDT 81.68 · 10 PDB
Residue 95: the brix domain; an α-helix

Full BRIX1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BRIX1 p.Ala120Val Uncertain significance ★ ⚠ same type
BRIX1 p.Ala26Gly Uncertain significance ★ ⚠ same type
BRIX1 p.Ala34Ser Uncertain significance ★ ⚠ same type
BRIX1 p.Ala36Glu Uncertain significance ★ ⚠ same type
BRIX1 p.Ala3Val Uncertain significance ★ ⚠ same type
BRIX1 p.Arg218Trp Uncertain significance ★ ⚠ same type
BRIX1 p.Arg267Leu Uncertain significance ★ ⚠ same type
BRIX1 p.Arg270Ile 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/brix1-p-asp95tyr (accessed [today's date]).

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