Is BROX p.Pro54Thr (c.160C>A) pathogenic?

BROX p.Pro54Thr (c.160C>A) is classified Benign in BROX (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-25). AlphaMissense: likely benign (0.0818); Low-frequency (popmax 2.32%, afr).

How common is BROX p.Pro54Thr (c.160C>A) in the general population?

BROX p.Pro54Thr (c.160C>A) is low-frequency (popmax 2.32%, afr) (gnomAD).

What do computational predictors say about BROX p.Pro54Thr (c.160C>A)?

AlphaMissense predicts likely benign (score 0.0818) — an in-silico prediction, not a clinical call.

BROX p.Pro54Thr

c.160C>A · rs73124896 · VCV787756

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0818 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.32%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0818	likely benign
REVEL	0.079	moderately benign-leaning
SaProt	LLR -7.37	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 5.9	GERP 1.7, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 17 kb · p 0.43 · regional, not allelic
Overall
CADD	20.3	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 2.32% African / African-American · 1,741/74,974 alleles

Filtering AF 2.23% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.19%

Overall 0.123% 1,990/1,613,812 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.32%	43
Middle Eastern	0.198%	505
Remaining individualsnot grpmax-eligible	0.189%	530
Admixed American	0.15%	666
South Asian	0.00769%	13,009
European (non-Finnish)	0.00186%	53,630

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.Pro54Thr
Coding: c.160C>A
MANE Select: NM_144695
dbSNP: rs73124896
Type: single nucleotide variant
Location: chr1:222718983 (GRCh38)
Gene constraint: LOEUF 1.123 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.15 · 7 PDB
Residue 54: 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 type
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-pro54thr (accessed [today's date]).

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