Is XRCC2 p.Phe192= (c.576T>C) pathogenic?

XRCC2 p.Phe192= (c.576T>C) is classified Likely benign in XRCC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-05-31). Very rare (popmax 0.00133%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with XRCC2 p.Phe192= (c.576T>C)?

XRCC2 p.Phe192= (c.576T>C) is associated with hereditary neoplastic syndrome (ClinVar).

How common is XRCC2 p.Phe192= (c.576T>C) in the general population?

XRCC2 p.Phe192= (c.576T>C) is very rare (popmax 0.00133%, afr) (gnomAD).

XRCC2 p.Phe192=

c.576T>C · VCV4866848

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

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 0.025	GERP 1.5, phastCons 0.12
Overall
CADD	7.355	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,046 alleles

Overall 6.2e-05% 1/1,614,166 alleles · very rare exomes 1/1,461,882 · genomes 0/152,284 · joint denominator

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.Phe192=
Coding: c.576T>C
MANE Select: NM_005431
Type: single nucleotide variant
Location: chr7:152648909 (GRCh38)
Gene constraint: LOEUF 1.209 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.57 · 16 PDB
Residue 192: a β-strand

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.Phe192Leu 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
XRCC2 p.Ala33Thr 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-phe192 (accessed [today's date]).

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