Is XRCC2 p.Arg7= (c.21G>A) pathogenic?

XRCC2 p.Arg7= (c.21G>A) is classified Likely benign in XRCC2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-02-15). Ultra-rare (popmax 0.0736%, sas); Associated with hereditary neoplastic syndrome.

What condition is associated with XRCC2 p.Arg7= (c.21G>A)?

XRCC2 p.Arg7= (c.21G>A) is associated with hereditary neoplastic syndrome (ClinVar).

How common is XRCC2 p.Arg7= (c.21G>A) in the general population?

XRCC2 p.Arg7= (c.21G>A) is ultra-rare (popmax 0.0736%, sas) (gnomAD).

XRCC2 p.Arg7=

c.21G>A · rs531499084 · VCV513404

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0736%, 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 0.38	GERP 1.8, phastCons 0.029
Overall
CADD	12.98	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0736% South Asian · 67/91,088 alleles

Filtering AF 0.0593% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0542%

Overall 0.00446% 72/1,613,866 alleles · ultra-rare exomes 68/1,461,506 · genomes 4/152,360 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0736%	1,360
Remaining individualsnot grpmax-eligible	0.0064%	15,622
European (non-Finnish)	8.48e-05%	1,179,806

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.Arg7=
Coding: c.21G>A
MANE Select: NM_005431
dbSNP: rs531499084
Type: single nucleotide variant
Location: chr7:152676059 (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.Arg7Gly Uncertain significance ★ ⚠ same residue
XRCC2 p.Arg7Lys 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-arg7 (accessed [today's date]).

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