Is XRCC2 p.Ser203= (c.609G>A) pathogenic?

XRCC2 p.Ser203= (c.609G>A) is classified Likely benign in XRCC2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-08). Very rare (popmax 0.00329%, sas); Associated with hereditary neoplastic syndrome.

What condition is associated with XRCC2 p.Ser203= (c.609G>A)?

XRCC2 p.Ser203= (c.609G>A) is associated with hereditary neoplastic syndrome (ClinVar).

How common is XRCC2 p.Ser203= (c.609G>A) in the general population?

XRCC2 p.Ser203= (c.609G>A) is very rare (popmax 0.00329%, sas) (gnomAD).

XRCC2 p.Ser203=

c.609G>A · rs542411586 · VCV1101036

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -12	GERP -13
Overall
CADD	0.033	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00329% South Asian · 3/91,062 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000479% 7/1,461,822 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,354
Remaining individualsnot grpmax-eligible	0.0016%	62,482
European (non-Finnish)	0.000254%	393,328

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: XRCC2
Protein: p.Ser203=
Coding: c.609G>A
MANE Select: NM_005431
dbSNP: rs542411586
Type: single nucleotide variant
Location: chr7:152648876 (GRCh38)
Gene constraint: LOEUF 1.209 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.57 · 16 PDB

Full XRCC2 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

XRCC2 p.Ser203Leu Uncertain significance ★★ ⚠ same residue
XRCC2 p.Ser203Ala Uncertain significance ★ ⚠ same residue
XRCC2 c.39+5G>C Uncertain significance ★★ same condition
XRCC2 p.Ala193Pro Uncertain significance ★★ ⚠ same condition
XRCC2 p.Ala193Val Uncertain significance ★★ ⚠ same condition
XRCC2 p.Ala202Val Uncertain significance ★★ ⚠ same condition
XRCC2 p.Ala212Val Uncertain significance ★★ ⚠ same condition
XRCC2 p.Ala33Pro Uncertain significance ★★ ⚠ 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/xrcc2-p-ser203 (accessed [today's date]).

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