Is BRIX1 p.Asn71Ser (c.212A>G) pathogenic?

BRIX1 p.Asn71Ser (c.212A>G) is classified Uncertain significance in BRIX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-15). AlphaMissense: likely benign (0.0621); Absent from gnomAD v4.1.

How common is BRIX1 p.Asn71Ser (c.212A>G) in the general population?

BRIX1 p.Asn71Ser (c.212A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BRIX1 p.Asn71Ser (c.212A>G)?

AlphaMissense predicts likely benign (score 0.0621) — an in-silico prediction, not a clinical call.

BRIX1 p.Asn71Ser

c.212A>G · VCV3993174

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0621 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0621	likely benign
REVEL	0.108	moderately benign-leaning
SaProt	LLR -6.77	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 9.2	GERP 0.82, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 9,753 bp · p 0.54 · regional, not allelic
Overall
CADD	18.43	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BRIX1
Protein: p.Asn71Ser
Coding: c.212A>G
MANE Select: NM_018321
Type: single nucleotide variant
Location: chr5:34918416 (GRCh38)
Gene constraint: LOEUF 0.626 · pLI 0.80 (gnomAD)
Structure: AlphaFold pLDDT 81.68 · 10 PDB
Residue 71: the brix domain

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-asn71ser (accessed [today's date]).

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