Is BRDT p.Ser615Pro (c.1843T>C) pathogenic?

BRDT p.Ser615Pro (c.1843T>C) is classified Uncertain significance in BRDT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-26). AlphaMissense: likely benign (0.1037); Absent from gnomAD v4.1.

How common is BRDT p.Ser615Pro (c.1843T>C) in the general population?

BRDT p.Ser615Pro (c.1843T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BRDT p.Ser615Pro (c.1843T>C)?

AlphaMissense predicts likely benign (score 0.1037) — an in-silico prediction, not a clinical call.

BRDT p.Ser615Pro

c.1843T>C · VCV4646651

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1037 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1037	likely benign
REVEL	0.017	moderately benign-leaning
SaProt	LLR -3.57	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 1.2	GERP 0.71, phastCons 0.17
Regional constraint	o/e 0.93	unconstrained · MANE · 52 kb · p 0.018 · regional, not allelic
Overall
CADD	13.94	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.Ser615Pro
Coding: c.1843T>C
MANE Select: NM_207189
Type: single nucleotide variant
Location: chr1:91981360 (GRCh38)
Gene constraint: LOEUF 0.801 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.40 · 22 PDB
Residue 615: the 'disordered' region

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

Similar variants

BRDT p.Ser615Cys Uncertain significance ★ ⚠ same residue
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

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-ser615pro (accessed [today's date]).

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