Is BRWD3 p.Pro1106= (c.3318A>G) pathogenic?

BRWD3 p.Pro1106= (c.3318A>G) is classified Benign/Likely benign in BRWD3 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2024-07-10). Ultra-rare (popmax 0.0521%, mid); Associated with Inborn genetic diseases.

What condition is associated with BRWD3 p.Pro1106= (c.3318A>G)?

BRWD3 p.Pro1106= (c.3318A>G) is associated with Inborn genetic diseases, intellectual disability, X-linked 93 (ClinVar).

How common is BRWD3 p.Pro1106= (c.3318A>G) in the general population?

BRWD3 p.Pro1106= (c.3318A>G) is ultra-rare (popmax 0.0521%, mid) (gnomAD).

BRWD3 p.Pro1106=

c.3318A>G · rs140203774 · VCV914754

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0521%, mid)

Conditions

Inborn genetic diseases

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 0.9	GERP -3.8, phastCons 1
Overall
CADD	8.67	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0521% Middle Eastern · 2/3,839 alleles

Filtering AF 0.017% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0161%

Overall 0.015% 180/1,203,500 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0521%	1,920
European (non-Finnish)	0.0194%	5,145
Remaining individualsnot grpmax-eligible	0.00634%	15,782
African / African-American	0.0035%	28,553

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.Pro1106=
Coding: c.3318A>G
MANE Select: NM_153252
dbSNP: rs140203774
Type: single nucleotide variant
Location: chrX:80692096 (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

Also linked: intellectual disability, X-linked 93

Similar variants

BRWD3 c.4006-1G>A Likely pathogenic ★★ same condition
BRWD3 p.Arg1240Ter Pathogenic/Likely pathogenic ★★ same condition
BRWD3 p.Arg190Ter Pathogenic ★★ same condition
BRWD3 c.2232-3T>C Uncertain significance ★★ same condition
BRWD3 c.90+5G>A Uncertain significance ★★ same condition
BRWD3 c.*2154A>G Uncertain significance ★★ same condition
BRWD3 c.*2877G>A Uncertain significance ★★ same condition
BRWD3 p.Ala123Val 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-pro1106 (accessed [today's date]).

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