Is BRIX1 p.Asn104Lys (c.312C>G) pathogenic?

BRIX1 p.Asn104Lys (c.312C>G) is classified Uncertain significance in BRIX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-29). AlphaMissense: likely pathogenic (0.9857); Very rare (popmax 0.000123%, nfe).

How common is BRIX1 p.Asn104Lys (c.312C>G) in the general population?

BRIX1 p.Asn104Lys (c.312C>G) is very rare (popmax 0.000123%, nfe) (gnomAD).

What do computational predictors say about BRIX1 p.Asn104Lys (c.312C>G)?

AlphaMissense predicts likely pathogenic (score 0.9857) — an in-silico prediction, not a clinical call.

BRIX1 p.Asn104Lys

c.312C>G · VCV3482490

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9857 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000123%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9857	likely pathogenic
REVEL	0.258	benign-leaning
SaProt	LLR -16.02	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.7	GERP -4
Regional constraint	o/e 0.97	unconstrained · MANE · 9,753 bp · p 0.54 · regional, not allelic
Overall
CADD	16.98	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 0.000123% European (non-Finnish) · 1/812,928 alleles

Overall 9.84e-05% 1/1,016,284 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: BRIX1
Protein: p.Asn104Lys
Coding: c.312C>G
MANE Select: NM_018321
Type: single nucleotide variant
Location: chr5:34919880 (GRCh38)
Gene constraint: LOEUF 0.626 · pLI 0.80 (gnomAD)
Structure: AlphaFold pLDDT 81.68 · 10 PDB
Residue 104: 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-asn104lys (accessed [today's date]).

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