Is BRWD3 p.Pro5Arg (c.14C>G) pathogenic?

BRWD3 p.Pro5Arg (c.14C>G) is classified Conflicting classifications of pathogenicity in BRWD3 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2023-09-10). AlphaMissense: ambiguous (0.4869); Rare (popmax 0.397%, sas); Associated with Inborn genetic diseases.

What condition is associated with BRWD3 p.Pro5Arg (c.14C>G)?

BRWD3 p.Pro5Arg (c.14C>G) is associated with Inborn genetic diseases (ClinVar).

How common is BRWD3 p.Pro5Arg (c.14C>G) in the general population?

BRWD3 p.Pro5Arg (c.14C>G) is rare (popmax 0.397%, sas) (gnomAD).

What do computational predictors say about BRWD3 p.Pro5Arg (c.14C>G)?

AlphaMissense predicts ambiguous (score 0.4869) — an in-silico prediction, not a clinical call.

BRWD3 p.Pro5Arg

c.14C>G · rs773723606 · VCV1773974

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4869 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.397%, sas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4869	ambiguous
REVEL	0.133	moderately benign-leaning
SaProt	LLR -9.20	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 64 kb · p 0.045 · regional, not allelic
Overall
CADD	26.2	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 0.397% South Asian · 210/52,853 alleles

Filtering AF 0.353% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.336%

Overall 0.0187% 218/1,166,923 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.397%	252
Remaining individualsnot grpmax-eligible	0.0131%	7,649
African / African-American	0.00179%	55,749
European (non-Finnish)	0.000115%	872,151

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: BRWD3
Protein: p.Pro5Arg
Coding: c.14C>G
MANE Select: NM_153252
dbSNP: rs773723606
Type: single nucleotide variant
Location: chrX:80809458 (GRCh38)
Structure: AlphaFold pLDDT 65.11

Full BRWD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BRWD3 c.2232-3T>C Uncertain significance ★★ same condition
BRWD3 p.Ala123Val Uncertain significance ★★ ⚠ same condition
BRWD3 p.Ala835Thr Uncertain significance ★★ ⚠ same condition
BRWD3 p.Arg1149Trp Uncertain significance ★★ ⚠ same condition
BRWD3 p.Arg1443Thr Uncertain significance ★★ ⚠ same condition
BRWD3 p.Arg1447Gln Uncertain significance ★★ ⚠ same condition
BRWD3 p.Arg1449Gly Uncertain significance ★★ ⚠ same condition
BRWD3 p.Arg1652Thr Uncertain significance ★★ ⚠ same condition

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/brwd3-p-pro5arg (accessed [today's date]).

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