Is BRMS1 p.Ser237Phe (c.710C>T) pathogenic?

BRMS1 p.Ser237Phe (c.710C>T) is classified Uncertain significance in BRMS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-08). AlphaMissense: likely benign (0.1698); Very rare (popmax 0.00134%, afr).

How common is BRMS1 p.Ser237Phe (c.710C>T) in the general population?

BRMS1 p.Ser237Phe (c.710C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about BRMS1 p.Ser237Phe (c.710C>T)?

AlphaMissense predicts likely benign (score 0.1698) — an in-silico prediction, not a clinical call.

BRMS1 p.Ser237Phe

c.710C>T · rs1415586092 · VCV2597587

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1698 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1698	likely benign
REVEL	0.176	moderately benign-leaning
SaProt	LLR -9.65	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 12	GERP 1.1, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 4,349 bp · p 0.25 · regional, not allelic
Overall
CADD	24.9	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

Grpmax group 0.00134% African / African-American · 1/74,894 alleles

Filtering AF 0.000501% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000745% 12/1,611,230 alleles · very rare exomes 11/1,459,002 · genomes 1/152,228 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,894
European (non-Finnish)	0.000933%	107,153

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: BRMS1
Protein: p.Ser237Phe
Coding: c.710C>T
MANE Select: NM_015399
dbSNP: rs1415586092
Type: single nucleotide variant
Location: chr11:66338266 (GRCh38)
Gene constraint: LOEUF 0.874 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.23 · 2 PDB

Full BRMS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BRMS1 p.Asp175= Benign ★★ same type
BRMS1 c.*105G>C Uncertain significance ★ same type
BRMS1 c.*111C>T Uncertain significance ★ same type
BRMS1 c.*113A>G Uncertain significance ★ same type
BRMS1 c.*122T>A Uncertain significance ★ same type
BRMS1 c.*126G>T Uncertain significance ★ same type
BRMS1 c.*135C>T Uncertain significance ★ same type
BRMS1 c.*167C>A 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/brms1-p-ser237phe (accessed [today's date]).

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