Is BRDT p.Phe98Leu (c.294C>A) pathogenic?

BRDT p.Phe98Leu (c.294C>A) is classified Uncertain significance in BRDT (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-22). AlphaMissense: likely pathogenic (0.6047); Very rare (popmax 0.00708%, sas).

How common is BRDT p.Phe98Leu (c.294C>A) in the general population?

BRDT p.Phe98Leu (c.294C>A) is very rare (popmax 0.00708%, sas) (gnomAD).

What do computational predictors say about BRDT p.Phe98Leu (c.294C>A)?

AlphaMissense predicts likely pathogenic (score 0.6047) — an in-silico prediction, not a clinical call.

BRDT p.Phe98Leu

c.294C>A · rs879020404 · VCV2528363

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6047 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00708%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6047	likely pathogenic
REVEL	0.121	moderately benign-leaning
SaProt	LLR -10.67	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	Δ0.22	donor loss · deltas
Constraint at this position
Conservation	phyloP -0.28	GERP -3.5, phastCons 0.12
Regional constraint	o/e 0.93	unconstrained · MANE · 52 kb · p 0.018 · regional, not allelic
Overall
CADD	15.03	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 0.00708% South Asian · 5/70,642 alleles

Filtering AF 0.00277% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.000374% 5/1,337,014 alleles · very rare

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: BRDT
Protein: p.Phe98Leu
Coding: c.294C>A
MANE Select: NM_207189
dbSNP: rs879020404
Type: single nucleotide variant
Location: chr1:91964728 (GRCh38)
Gene constraint: LOEUF 0.801 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.40 · 22 PDB
Residue 98: the bromo 1 domain; an α-helix

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

Similar variants

BRDT p.Gln795Ter Likely pathogenic ★ same type
BRDT p.Ala241Val Uncertain significance ★ ⚠ same type
BRDT p.Ala405Thr Uncertain significance ★ ⚠ same type
BRDT p.Ala898Gly Uncertain significance ★ ⚠ same type
BRDT p.Arg419Gln Uncertain significance ★ ⚠ same type
BRDT p.Arg422Cys Uncertain significance ★ ⚠ same type
BRDT p.Arg422Leu Uncertain significance ★ ⚠ same type
BRDT p.Arg446Cys 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/brdt-p-phe98leu (accessed [today's date]).

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