Is RAD51D p.Ser299Phe (c.896C>T) pathogenic?

RAD51D p.Ser299Phe (c.896C>T) is classified Uncertain significance in RAD51D (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-12-04). AlphaMissense: ambiguous (0.3681); Very rare (popmax 0.0022%, sas); Associated with hereditary neoplastic syndrome.

What condition is associated with RAD51D p.Ser299Phe (c.896C>T)?

RAD51D p.Ser299Phe (c.896C>T) is associated with hereditary neoplastic syndrome (ClinVar).

How common is RAD51D p.Ser299Phe (c.896C>T) in the general population?

RAD51D p.Ser299Phe (c.896C>T) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about RAD51D p.Ser299Phe (c.896C>T)?

AlphaMissense predicts ambiguous (score 0.3681) — an in-silico prediction, not a clinical call.

RAD51D p.Ser299Phe

c.896C>T · rs1379526157 · VCV926859

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3681 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.3681	ambiguous
REVEL	0.271	benign-leaning
SaProt	LLR -9.23	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 1.5, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 19 kb · p 0.24 · regional, not allelic
Overall
CADD	27.3	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

Grpmax group 0.0022% South Asian · 2/91,084 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000137% 2/1,461,836 alleles · very rare

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: RAD51D
Protein: p.Ser299Phe
Coding: c.896C>T
MANE Select: NM_002878
dbSNP: rs1379526157
Type: single nucleotide variant
Location: chr17:35101208 (GRCh38)
Gene constraint: LOEUF 1.092 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 88.64 · 17 PDB
Residue 299: a β-strand

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 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
RAD51D c.739-1G>A Likely pathogenic ★★ same condition
RAD51D c.82+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/rad51d-p-ser299phe (accessed [today's date]).

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