Is RAD51 p.Phe92Ser (c.275T>C) pathogenic?

RAD51 p.Phe92Ser (c.275T>C) is classified Uncertain significance in RAD51 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-05). AlphaMissense: likely pathogenic (0.9145); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with RAD51 p.Phe92Ser (c.275T>C)?

RAD51 p.Phe92Ser (c.275T>C) is associated with Inborn genetic diseases (ClinVar).

How common is RAD51 p.Phe92Ser (c.275T>C) in the general population?

RAD51 p.Phe92Ser (c.275T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RAD51 p.Phe92Ser (c.275T>C)?

AlphaMissense predicts likely pathogenic (score 0.9145) — an in-silico prediction, not a clinical call.

RAD51 p.Phe92Ser

c.275T>C · rs2504436533 · VCV2450864

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9145 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9145	likely pathogenic
REVEL	0.49	indeterminate
SaProt	LLR -11.90	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.7, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 7,535 bp · p 0.0023 · regional, not allelic
Overall
CADD	23.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: RAD51
Protein: p.Phe92Ser
Coding: c.275T>C
MANE Select: NM_002875
dbSNP: rs2504436533
Type: single nucleotide variant
Location: chr15:40706226 (GRCh38)
Gene constraint: LOEUF 0.467 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 91.59 · 52 PDB
Residue 92: an α-helix

Full RAD51 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RAD51 p.Ala157Thr Uncertain significance ★★ ⚠ same condition
RAD51 p.Ala209Thr Uncertain significance ★★ same condition
RAD51 p.Ala256Thr Uncertain significance ★★ ⚠ same condition
RAD51 p.Ala328Ser Uncertain significance ★★ ⚠ same condition
RAD51 p.Ala79Val Uncertain significance ★★ ⚠ same condition
RAD51 p.Arg130Gly Uncertain significance ★★ ⚠ same condition
RAD51 p.Arg150Trp Uncertain significance ★★ ⚠ same condition
RAD51 p.Arg254Gln Uncertain significance ★★ same condition

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/rad51-p-phe92ser (accessed [today's date]).

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