Is BRD2 p.Leu238Phe (c.712C>T) pathogenic?

BRD2 p.Leu238Phe (c.712C>T) is classified Benign in BRD2 (ClinVar, Single submitter, 2 submitters; last evaluated 2019-12-31). AlphaMissense: likely benign (0.1336); Rare (popmax 0.478%, mid).

How common is BRD2 p.Leu238Phe (c.712C>T) in the general population?

BRD2 p.Leu238Phe (c.712C>T) is rare (popmax 0.478%, mid) (gnomAD).

What do computational predictors say about BRD2 p.Leu238Phe (c.712C>T)?

AlphaMissense predicts likely benign (score 0.1336) — an in-silico prediction, not a clinical call.

BRD2 p.Leu238Phe

c.712C>T · rs176250 · VCV785805

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1336 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.478%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1336	likely benign
REVEL	0.106	moderately benign-leaning
SaProt	LLR -8.33	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 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 1.23	unconstrained · MANE · 3,664 bp · p 2.1e-05 · regional, not allelic
Overall
CADD	23.0	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 0.478% Middle Eastern · 29/6,062 alleles

Filtering AF 0.443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.439%

Overall 0.462% 7,459/1,613,072 alleles · rare exomes 6,730/1,460,762 · genomes 729/152,310 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	7.79%	13
Ashkenazi Jewishnot grpmax-eligible	3.72%	27
Remaining individualsnot grpmax-eligible	0.568%	176
Middle Easterngrpmax	0.478%	209
European (non-Finnish)	0.453%	221
Finnishnot grpmax-eligible	0.342%	293
South Asian	0.214%	467
Admixed American	0.145%	690
African / African-American	0.0746%	1,340
East Asian	0.00891%	11,222

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: BRD2
Protein: p.Leu238Phe
Coding: c.712C>T
MANE Select: NM_005104
dbSNP: rs176250
Type: single nucleotide variant
Location: chr6:32976351 (GRCh38)
Gene constraint: LOEUF 0.28 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 65.70 · 169 PDB
Residue 238: a UniProt-annotated variant site (in)

Full BRD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BRD2 p.Pro12Leu Uncertain significance ★★ ⚠ same type
BRD2 p.Ala766Thr Benign/Likely benign ★★ same type
BRD2 p.Gln533= Likely benign ★★ same type
BRD2 p.Leu383= Likely benign ★★ same type
BRD2 p.Ser397= Benign/Likely benign ★★ same type
BRD2 p.Val465= Likely benign ★★ same type
BRD2 p.Ala263Val Uncertain significance ★ ⚠ same type
BRD2 p.Ala295Pro 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/brd2-p-leu238phe (accessed [today's date]).

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