Is BRMS1 p.Asp175= (c.525C>T) pathogenic?

BRMS1 p.Asp175= (c.525C>T) is classified Benign in BRMS1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-02-26). Common (popmax 5.37%, afr) — too common for a highly-penetrant pathogenic allele.

BRMS1 p.Asp175=

Q: How common is BRMS1 p.Asp175= (c.525C>T) in the general population?

BRMS1 p.Asp175= (c.525C>T) is common (popmax 5.37%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.525C>T · rs17850564 · VCV776630

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 5.37%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.16	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP -1.1, phastCons 1
Overall
CADD	11.93	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.37% African / African-American · 4,025/74,984 alleles

Filtering AF 5.23% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.17%

Overall 0.278% 4,484/1,611,942 alleles · common exomes 2,220/1,459,652 · genomes 2,264/152,290 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.37%	19
Admixed American	0.33%	303
Remaining individualsnot grpmax-eligible	0.321%	312
Middle Eastern	0.111%	904
South Asian	0.0154%	6,496
European (non-Finnish)	0.00348%	28,775

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.Asp175=
Coding: c.525C>T
MANE Select: NM_015399
dbSNP: rs17850564
Type: single nucleotide variant
Location: chr11:66340784 (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 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
BRMS1 c.*177C>T 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-asp175 (accessed [today's date]).

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