Is BROX p.Ala169= (c.507G>A) pathogenic?

BROX p.Ala169= (c.507G>A) is classified Benign in BROX (ClinVar, Single submitter, 2 submitters; last evaluated 2018-07-17). Common (popmax 7.76%, eas) — too common for a highly-penetrant pathogenic allele.

BROX p.Ala169=

Q: How common is BROX p.Ala169= (c.507G>A) in the general population?

BROX p.Ala169= (c.507G>A) is common (popmax 7.76%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.507G>A · rs17163847 · VCV780093

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 7.76%, eas) — 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.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -0.45, phastCons 0.98
Overall
CADD	13.15	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.76% East Asian · 3,474/44,752 alleles

Filtering AF 7.55% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.46%

Overall 0.279% 4,497/1,611,902 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	7.76%	13
Remaining individualsnot grpmax-eligible	0.458%	218
Finnishnot grpmax-eligible	0.421%	238
South Asian	0.142%	703
Middle Eastern	0.0495%	2,019
Admixed American	0.0369%	2,710
European (non-Finnish)	0.0255%	3,918
African / African-American	0.0174%	5,757

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: BROX
Protein: p.Ala169=
Coding: c.507G>A
MANE Select: NM_144695
dbSNP: rs17163847
Type: single nucleotide variant
Location: chr1:222725482 (GRCh38)
Gene constraint: LOEUF 1.123 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.15 · 7 PDB
Residue 169: the bro1 domain; an α-helix

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

Similar variants

BROX p.Ala169Val Uncertain significance ★ ⚠ same residue
BROX p.Ala191Val Uncertain significance ★ ⚠ same type
BROX p.Ala213Val Uncertain significance ★ ⚠ same type
BROX p.Arg178Gln Uncertain significance ★ ⚠ same type
BROX p.Arg378Lys Uncertain significance ★ ⚠ same type
BROX p.Asn117Ser Uncertain significance ★ ⚠ same type
BROX p.Asn19Ser Uncertain significance ★ ⚠ same type
BROX p.Asn218Ser 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/brox-p-ala169 (accessed [today's date]).

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