Is RAD51D p.Ala172Pro (c.514G>C) pathogenic?

RAD51D p.Ala172Pro (c.514G>C) is classified Uncertain significance in RAD51D (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-24). AlphaMissense: ambiguous (0.4905); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with RAD51D p.Ala172Pro (c.514G>C)?

RAD51D p.Ala172Pro (c.514G>C) is associated with hereditary neoplastic syndrome (ClinVar).

How common is RAD51D p.Ala172Pro (c.514G>C) in the general population?

RAD51D p.Ala172Pro (c.514G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RAD51D p.Ala172Pro (c.514G>C)?

AlphaMissense predicts ambiguous (score 0.4905) — an in-silico prediction, not a clinical call.

RAD51D p.Ala172Pro

c.514G>C · VCV4844320

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4905 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.4905	ambiguous
REVEL	0.254	benign-leaning
SaProt	LLR -11.06	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 1.5, phastCons 0.67
Regional constraint	o/e 0.94	unconstrained · MANE · 19 kb · p 0.24 · regional, not allelic
Overall
CADD	21.9	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: RAD51D
Protein: p.Ala172Pro
Coding: c.514G>C
MANE Select: NM_002878
Type: single nucleotide variant
Location: chr17:35106448 (GRCh38)
Gene constraint: LOEUF 1.092 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 88.64 · 17 PDB

Full RAD51D gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RAD51D p.Ala172Val Uncertain significance ★★ ⚠ same residue
RAD51D p.Ala172= Benign/Likely benign ★★ same residue
RAD51D c.144+1G>T Pathogenic/Likely pathogenic ★★ same condition
RAD51D c.264-2A>G Pathogenic/Likely pathogenic ★★ same condition
RAD51D c.346-1G>C Pathogenic/Likely pathogenic ★★ same condition
RAD51D c.576+1G>A Pathogenic/Likely pathogenic ★★ same condition
RAD51D c.738+1G>A Pathogenic/Likely pathogenic ★★ same condition
RAD51D c.738+1G>T 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/rad51d-p-ala172pro (accessed [today's date]).

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