Is BRD10 p.Pro100His (c.299C>A) pathogenic?

BRD10 p.Pro100His (c.299C>A) is classified Uncertain significance in BRD10 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-01). AlphaMissense: likely pathogenic (0.7839); Very rare (popmax 0.00167%, amr).

How common is BRD10 p.Pro100His (c.299C>A) in the general population?

BRD10 p.Pro100His (c.299C>A) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about BRD10 p.Pro100His (c.299C>A)?

AlphaMissense predicts likely pathogenic (score 0.7839) — an in-silico prediction, not a clinical call.

BRD10 p.Pro100His

c.299C>A · rs765774351 · VCV2492235

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7839 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7839	likely pathogenic
REVEL	0.24	benign-leaning
SaProt	LLR -8.54	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 1.20	unconstrained · MANE · 39 kb · p 3.1e-06 · regional, not allelic
Overall
CADD	29.0	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 0.00167% Admixed American · 1/59,928 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000248% 4/1,612,062 alleles · very rare exomes 3/1,459,846 · genomes 1/152,216 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,928
South Asian	0.0011%	91,006
European (non-Finnish)	0.00017%	589,598

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: BRD10
Protein: p.Pro100His
Coding: c.299C>A
MANE Select: NM_001017969
dbSNP: rs765774351
Type: single nucleotide variant
Location: chr9:6007489 (GRCh38)
Structure: AlphaFold pLDDT 46.10
Residue 100: the bromo domain

Full BRD10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BRD10 p.Pro1552= Benign ★★ same type
BRD10 p.Val1306Leu Likely benign ★★ same type
BRD10 p.Ala1032Pro Uncertain significance ★ ⚠ same type
BRD10 p.Ala1150Thr Uncertain significance ★ ⚠ same type
BRD10 p.Ala116Val Uncertain significance ★ ⚠ same type
BRD10 p.Ala1182Gly Uncertain significance ★ ⚠ same type
BRD10 p.Ala1225Gly Uncertain significance ★ ⚠ same type
BRD10 p.Ala1256Val 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/brd10-p-pro100his (accessed [today's date]).

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