Is BRDT p.Ser185Phe (c.554C>T) pathogenic?

BRDT p.Ser185Phe (c.554C>T) is classified Uncertain significance in BRDT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-09). AlphaMissense: likely benign (0.1076); Absent from gnomAD v4.1.

How common is BRDT p.Ser185Phe (c.554C>T) in the general population?

BRDT p.Ser185Phe (c.554C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BRDT p.Ser185Phe (c.554C>T)?

AlphaMissense predicts likely benign (score 0.1076) — an in-silico prediction, not a clinical call.

BRDT p.Ser185Phe

c.554C>T · VCV4216134

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1076 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1076	likely benign
REVEL	0.024	moderately benign-leaning
SaProt	LLR -8.41	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 0.34	GERP 0.97
Regional constraint	o/e 0.93	unconstrained · MANE · 52 kb · p 0.018 · regional, not allelic
Overall
CADD	15.53	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BRDT
Protein: p.Ser185Phe
Coding: c.554C>T
MANE Select: NM_207189
Type: single nucleotide variant
Location: chr1:91976374 (GRCh38)
Gene constraint: LOEUF 0.801 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.40 · 22 PDB

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-ser185phe (accessed [today's date]).

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