Is RAD51C p.Pro145= (c.435A>G) pathogenic?

RAD51C p.Pro145= (c.435A>G) is classified Conflicting classifications of pathogenicity in RAD51C (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2025-12-08). Very rare (popmax 0.00891%, eas); Associated with Fanconi anemia complementation group O.

What condition is associated with RAD51C p.Pro145= (c.435A>G)?

RAD51C p.Pro145= (c.435A>G) is associated with Fanconi anemia complementation group O, breast-ovarian cancer, familial, susceptibility to, 3, hereditary neoplastic syndrome (ClinVar).

How common is RAD51C p.Pro145= (c.435A>G) in the general population?

RAD51C p.Pro145= (c.435A>G) is very rare (popmax 0.00891%, eas) (gnomAD).

RAD51C p.Pro145=

c.435A>G · rs555235745 · VCV492368

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Conditions

Fanconi anemia complementation group O

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.537	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.83	GERP -0.92, phastCons 0.96
Overall
CADD	11.86	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00891% East Asian · 4/44,880 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.000372% 6/1,614,232 alleles · very rare exomes 4/1,461,876 · genomes 2/152,356 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,220
European (non-Finnish)	0.000169%	590,016

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: RAD51C
Protein: p.Pro145=
Coding: c.435A>G
MANE Select: NM_058216
dbSNP: rs555235745
Type: single nucleotide variant
Location: chr17:58696723 (GRCh38)
Gene constraint: LOEUF 1.139 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 84.23 · 17 PDB

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.Pro145Leu Uncertain significance ★★ ⚠ same residue
RAD51C p.Pro145Ser Uncertain significance ★★ ⚠ same residue
RAD51C p.Pro145Ala Uncertain significance ★ ⚠ same residue
RAD51C p.Pro145Thr Uncertain significance ★ ⚠ same residue
RAD51C p.Pro145fs Pathogenic/Likely pathogenic ★★ 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

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-pro145 (accessed [today's date]).

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