Is RAD51C p.Ser331fs (c.990del) pathogenic?

RAD51C p.Ser331fs (c.990del) is classified Likely pathogenic in RAD51C (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-21). No gnomAD frequency available for this variant; Associated with Fanconi anemia complementation group O.

What condition is associated with RAD51C p.Ser331fs (c.990del)?

RAD51C p.Ser331fs (c.990del) is associated with Fanconi anemia complementation group O, breast-ovarian cancer, familial, susceptibility to, 3, hereditary neoplastic syndrome (ClinVar).

How common is RAD51C p.Ser331fs (c.990del) in the general population?

RAD51C p.Ser331fs (c.990del) is no gnomAD frequency available for this variant (gnomAD).

RAD51C p.Ser331fs

c.990del · rs2509364078 · VCV2722040

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Fanconi anemia complementation group O

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	escapes	premature termination codon within the last 50 nt of the penultimate exon (8 of 9, 38 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.8	GERP 0.79, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: RAD51C
Protein: p.Ser331fs
Coding: c.990del
MANE Select: NM_058216
dbSNP: rs2509364078
Type: Deletion
Location: chr17:58732506 (GRCh38)
Gene constraint: LOEUF 1.139 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 84.23 · 17 PDB
Residue 331: a β-strand

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: breast-ovarian cancer, familial, susceptibility to, 3 hereditary neoplastic syndrome

Similar variants

RAD51C p.Ser331Thr Uncertain significance ★★ ⚠ same residue
RAD51C p.Ser331Arg Uncertain significance ★ ⚠ same residue
RAD51C p.Ser331Asn Uncertain significance ★ ⚠ same residue
RAD51C p.Ser331Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
RAD51C p.Ser331= Likely benign ★ same residue
RAD51C c.1026+5_1026+7del Pathogenic/Likely pathogenic ★★ same condition
RAD51C c.146-4_146-2del Likely pathogenic ★★ same condition
RAD51C c.407_420del14 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-ser331fs (accessed [today's date]).

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