Is XPA p.Lys89Thr (c.266A>C) pathogenic?

XPA p.Lys89Thr (c.266A>C) is classified Uncertain significance in XPA (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-10). AlphaMissense: likely benign (0.08); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with XPA p.Lys89Thr (c.266A>C)?

XPA p.Lys89Thr (c.266A>C) is associated with Inborn genetic diseases (ClinVar).

How common is XPA p.Lys89Thr (c.266A>C) in the general population?

XPA p.Lys89Thr (c.266A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about XPA p.Lys89Thr (c.266A>C)?

AlphaMissense predicts likely benign (score 0.08) — an in-silico prediction, not a clinical call.

XPA p.Lys89Thr

c.266A>C · rs2490237610 · VCV2242642

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.08 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.08	likely benign
REVEL	0.062	moderately benign-leaning
SaProt	LLR -6.44	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 3.5	GERP 2, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 22 kb · p 0.54 · regional, not allelic
Overall
CADD	19.92	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: XPA
Protein: p.Lys89Thr
Coding: c.266A>C
MANE Select: NM_000380
dbSNP: rs2490237610
Type: single nucleotide variant
Location: chr9:97693666 (GRCh38)
Gene constraint: LOEUF 1.068 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.51 · 18 PDB
Residue 89: the 'interaction with cep164 and required for uv resistance' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

XPA c.555+8A>G Pathogenic ★★ same condition
XPA p.Glu245Lys Uncertain significance ★★ ⚠ same condition
XPA p.Met118Thr Uncertain significance ★★ ⚠ same condition
XPA p.Thr51Arg Uncertain significance ★★ ⚠ same condition
XPA p.Tyr116= Likely benign ★★ same condition
XPA p.Ala144Thr Uncertain significance ★ ⚠ same condition
XPA p.Ala22Ser Uncertain significance ★ ⚠ same condition
XPA p.Ala4Val 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/xpa-p-lys89thr (accessed [today's date]).

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