Is BRD7 p.Ser46Pro (c.136T>C) pathogenic?

BRD7 p.Ser46Pro (c.136T>C) is classified Uncertain significance in BRD7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-28). AlphaMissense: likely benign (0.1694); Ultra-rare (popmax 0.0395%, sas).

How common is BRD7 p.Ser46Pro (c.136T>C) in the general population?

BRD7 p.Ser46Pro (c.136T>C) is ultra-rare (popmax 0.0395%, sas) (gnomAD).

What do computational predictors say about BRD7 p.Ser46Pro (c.136T>C)?

AlphaMissense predicts likely benign (score 0.1694) — an in-silico prediction, not a clinical call.

BRD7 p.Ser46Pro

c.136T>C · rs201842421 · VCV2522638

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1694 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0395%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1694	likely benign
REVEL	0.061	moderately benign-leaning
SaProt	LLR -8.01	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 11	GERP 1.7, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 14 kb · p 0.18 · regional, not allelic
Overall
CADD	24.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0395% South Asian · 36/91,080 alleles

Filtering AF 0.0293% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0258%

Overall 0.0193% 312/1,614,140 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0395%	2,530
European (non-Finnish)	0.0222%	4,504
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0144%	6,945
Finnishnot grpmax-eligible	0.00469%	21,337
Admixed American	0.00167%	60,030

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: BRD7
Protein: p.Ser46Pro
Coding: c.136T>C
MANE Select: NM_013263
dbSNP: rs201842421
Type: single nucleotide variant
Location: chr16:50368212 (GRCh38)
Gene constraint: LOEUF 0.336 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 64.87 · 11 PDB
Residue 46: the 'disordered' region

Full BRD7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BRD7 p.Ala101Thr Uncertain significance ★ ⚠ same type
BRD7 p.Ala284Val Uncertain significance ★ ⚠ same type
BRD7 p.Ala520Val Uncertain significance ★ ⚠ same type
BRD7 p.Ala559Thr Uncertain significance ★ ⚠ same type
BRD7 p.Arg254Gln Uncertain significance ★ ⚠ same type
BRD7 p.Arg276Ile Uncertain significance ★ ⚠ same type
BRD7 p.Arg276Lys Uncertain significance ★ ⚠ same type
BRD7 p.Arg63Pro 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/brd7-p-ser46pro (accessed [today's date]).

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