Is XK p.Pro99Ser (c.295C>T) pathogenic?

XK p.Pro99Ser (c.295C>T) is classified Likely benign in XK (ClinVar, Single submitter, 1 submitter; last evaluated 2019-01-09). AlphaMissense: ambiguous (0.5441); Absent from gnomAD v4.1.

How common is XK p.Pro99Ser (c.295C>T) in the general population?

XK p.Pro99Ser (c.295C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about XK p.Pro99Ser (c.295C>T)?

AlphaMissense predicts ambiguous (score 0.5441) — an in-silico prediction, not a clinical call.

XK p.Pro99Ser

c.295C>T · VCV4949648

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5441 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.5441	ambiguous
REVEL	0.455	indeterminate
SaProt	LLR -6.00	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 42 kb · p 8.3e-09 · regional, not allelic
Overall
CADD	24.9	PHRED · no single calibrated threshold — expert panels disagree

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: XK
Protein: p.Pro99Ser
Coding: c.295C>T
MANE Select: NM_021083
Type: single nucleotide variant
Location: chrX:37694335 (GRCh38)
Structure: AlphaFold pLDDT 81.89 · 1 PDB

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

Similar variants

XK p.Pro99= Likely benign ★★ same residue
XK p.Pro99Ala Uncertain significance ★ ⚠ same residue
XK p.Arg133Ter Pathogenic ★★ same type
XK p.Arg222Ter Pathogenic/Likely pathogenic ★★ same type
XK p.Arg138Trp Uncertain significance ★★ ⚠ same type
XK p.Asn244Ser Uncertain significance ★★ ⚠ same type
XK p.Glu265Gly Uncertain significance ★★ ⚠ same type
XK p.Leu185Ser 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/xk-p-pro99ser (accessed [today's date]).

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