Is BRD7 p.Phe49Leu (c.147C>G) pathogenic?

BRD7 p.Phe49Leu (c.147C>G) is classified Likely benign in BRD7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-01). AlphaMissense: likely pathogenic (0.6183); Rare (popmax 0.39%, nfe).

How common is BRD7 p.Phe49Leu (c.147C>G) in the general population?

BRD7 p.Phe49Leu (c.147C>G) is rare (popmax 0.39%, nfe) (gnomAD).

What do computational predictors say about BRD7 p.Phe49Leu (c.147C>G)?

AlphaMissense predicts likely pathogenic (score 0.6183) — an in-silico prediction, not a clinical call.

BRD7 p.Phe49Leu

c.147C>G · rs145220538 · VCV2646508

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6183 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.39%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6183	likely pathogenic
REVEL	0.058	moderately benign-leaning
SaProt	LLR -4.74	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 2.4	GERP -1.2, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 14 kb · p 0.18 · regional, not allelic
Overall
CADD	16.98	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 0.39% European (non-Finnish) · 4,599/1,180,030 alleles

Filtering AF 0.38% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.376%

Overall 0.31% 5,000/1,614,116 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.39%	257
Remaining individualsnot grpmax-eligible	0.186%	539
Finnishnot grpmax-eligible	0.173%	577
Ashkenazi Jewishnot grpmax-eligible	0.138%	722
Middle Eastern	0.0825%	1,212
Admixed American	0.0633%	1,580
African / African-American	0.0613%	1,631
South Asian	0.0483%	2,070

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.Phe49Leu
Coding: c.147C>G
MANE Select: NM_013263
dbSNP: rs145220538
Type: single nucleotide variant
Location: chr16:50368201 (GRCh38)
Gene constraint: LOEUF 0.336 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 64.87 · 11 PDB
Residue 49: 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-phe49leu (accessed [today's date]).

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