Is RAD52 p.Ser418Pro (c.1252T>C) pathogenic?

RAD52 p.Ser418Pro (c.1252T>C) is classified Uncertain significance in RAD52 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-28). AlphaMissense: likely benign (0.141); Very rare (popmax 0.0044%, sas).

How common is RAD52 p.Ser418Pro (c.1252T>C) in the general population?

RAD52 p.Ser418Pro (c.1252T>C) is very rare (popmax 0.0044%, sas) (gnomAD).

What do computational predictors say about RAD52 p.Ser418Pro (c.1252T>C)?

AlphaMissense predicts likely benign (score 0.141) — an in-silico prediction, not a clinical call.

RAD52 p.Ser418Pro

c.1252T>C · rs546745829 · VCV2461211

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.141 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0044%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.141	likely benign
REVEL	0.119	moderately benign-leaning
SaProt	LLR -7.08	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.3	GERP -3.4, phastCons 0.42
Regional constraint	o/e 0.90	unconstrained · MANE · 20 kb · p 0.017 · regional, not allelic
Overall
CADD	20.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0044% South Asian · 4/90,832 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000893%

Overall 0.000686% 11/1,604,652 alleles · very rare exomes 10/1,452,346 · genomes 1/152,306 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0044%	22,708
European (non-Finnish)	0.000597%	167,374

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: RAD52
Protein: p.Ser418Pro
Coding: c.1252T>C
MANE Select: NM_134424
dbSNP: rs546745829
Type: single nucleotide variant
Location: chr12:913396 (GRCh38)
Gene constraint: LOEUF 1.185 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.52 · 11 PDB
Residue 418: the 'disordered' region

Full RAD52 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RAD52 p.Gln221Glu Benign ★★ same type
RAD52 p.Tyr415Ter Likely benign ★★ same type
RAD52 c.84+1G>A Uncertain significance ★ same type
RAD52 p.Arg180Cys Uncertain significance ★ ⚠ same type
RAD52 p.Arg204Thr Uncertain significance ★ ⚠ same type
RAD52 p.Arg271Trp Uncertain significance ★ ⚠ same type
RAD52 p.Asn99Ser Uncertain significance ★ ⚠ same type
RAD52 p.Gln30Pro 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/rad52-p-ser418pro (accessed [today's date]).

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