Is RAD51B p.Pro35= (c.105A>C) pathogenic?

RAD51B p.Pro35= (c.105A>C) is classified Likely benign in RAD51B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-27). Very rare (popmax 0.00669%, eas).

How common is RAD51B p.Pro35= (c.105A>C) in the general population?

RAD51B p.Pro35= (c.105A>C) is very rare (popmax 0.00669%, eas) (gnomAD).

RAD51B p.Pro35=

c.105A>C · VCV3786464

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00669%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -1.4	GERP -2.3
Overall
CADD	5.904	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00669% East Asian · 3/44,848 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000892%

Overall 0.000186% 3/1,612,738 alleles · very rare exomes 2/1,460,592 · genomes 1/152,146 · joint denominator

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: RAD51B
Protein: p.Pro35=
Coding: c.105A>C
MANE Select: NM_133510
Type: single nucleotide variant
Location: chr14:67825484 (GRCh38)
Gene constraint: LOEUF 1.247 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 79.50 · 5 PDB
Residue 35: the 'interaction with rad51c' region; an α-helix

Full RAD51B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RAD51B p.Pro35Ala Uncertain significance ★ ⚠ same residue
RAD51B p.Pro35Leu Uncertain significance ★ ⚠ same residue
RAD51B p.Pro35Ser Uncertain significance ★ ⚠ same residue
RAD51B c.315+2T>A Uncertain significance ★★ same type
RAD51B p.Ala146Thr Uncertain significance ★★ ⚠ same type
RAD51B p.Ala268Pro Uncertain significance ★★ ⚠ same type
RAD51B p.Arg47Ter Uncertain significance ★★ same type
RAD51B p.Pro326Ala 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/rad51b-p-pro35 (accessed [today's date]).

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