Is RAD51C p.Ala175Ser (c.523G>T) pathogenic?

RAD51C p.Ala175Ser (c.523G>T) is classified Conflicting classifications of pathogenicity in RAD51C (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-10-28). AlphaMissense: likely benign (0.106); Absent from gnomAD v4.1; Associated with Fanconi anemia complementation group O.

What condition is associated with RAD51C p.Ala175Ser (c.523G>T)?

RAD51C p.Ala175Ser (c.523G>T) is associated with Fanconi anemia complementation group O, hereditary neoplastic syndrome (ClinVar).

How common is RAD51C p.Ala175Ser (c.523G>T) in the general population?

RAD51C p.Ala175Ser (c.523G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RAD51C p.Ala175Ser (c.523G>T)?

AlphaMissense predicts likely benign (score 0.106) — an in-silico prediction, not a clinical call.

RAD51C p.Ala175Ser

c.523G>T · rs587780838 · VCV487201

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.106 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Fanconi anemia complementation group O

Computational evidence

Protein change
AlphaMissense	0.106	likely benign
REVEL	0.234	benign-leaning
SaProt	LLR -5.37	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 8.6	GERP 0.51, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 42 kb · p 0.31 · regional, not allelic
Overall
CADD	27.1	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

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: RAD51C
Protein: p.Ala175Ser
Coding: c.523G>T
MANE Select: NM_058216
dbSNP: rs587780838
Type: single nucleotide variant
Location: chr17:58696811 (GRCh38)
Gene constraint: LOEUF 1.139 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 84.23 · 17 PDB
Residue 175: a UniProt-annotated variant site (in); an α-helix

Full RAD51C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Fanconi anemia complementation group O — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome

Similar variants

RAD51C p.Ala175Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
RAD51C p.Ala175Val Uncertain significance ★ ⚠ same residue
RAD51C c.145+1G>A Pathogenic/Likely pathogenic ★★ same condition
RAD51C c.145+1G>T Pathogenic/Likely pathogenic ★★ same condition
RAD51C c.146-1G>A Likely pathogenic ★★ same condition
RAD51C c.404+1G>A Likely pathogenic ★★ same condition
RAD51C c.404+2T>C Pathogenic/Likely pathogenic ★★ same condition
RAD51C c.405-1G>A Pathogenic/Likely pathogenic ★★ 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/rad51c-p-ala175ser (accessed [today's date]).

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