Is ALG13 p.Cys265Phe (c.794G>T) pathogenic?

ALG13 p.Cys265Phe (c.794G>T) is classified Uncertain significance in ALG13 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-06-02). AlphaMissense: likely pathogenic (0.9427); Absent from gnomAD v4.1; Associated with ALG13-related disorder.

What condition is associated with ALG13 p.Cys265Phe (c.794G>T)?

ALG13 p.Cys265Phe (c.794G>T) is associated with ALG13-related disorder (ClinVar).

How common is ALG13 p.Cys265Phe (c.794G>T) in the general population?

ALG13 p.Cys265Phe (c.794G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ALG13 p.Cys265Phe (c.794G>T)?

AlphaMissense predicts likely pathogenic (score 0.9427) — an in-silico prediction, not a clinical call.

ALG13 p.Cys265Phe

c.794G>T · VCV3345074

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9427 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

ALG13-related disorder

Computational evidence

Protein change
AlphaMissense	0.9427	likely pathogenic · top 7% in ALG13
REVEL	0.619	indeterminate
SaProt	LLR -15.09	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 5.4, phastCons 1
Regional constraint	o/e 0.28	constrained · MANE · 698 bp · p 5.1e-05 · regional, not allelic
Overall
CADD	26.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: ALG13
Protein: p.Cys265Phe
Coding: c.794G>T
MANE Select: NM_001099922
Type: single nucleotide variant
Location: chrX:111709008 (GRCh38)
Structure: AlphaFold pLDDT 54.42
Residue 265: the otu domain; the 'deubiquitinase activity' region

Full ALG13 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ALG13-related disorder

Similar variants

ALG13 p.Cys265= Likely benign ★ same residue
ALG13 p.Asn107Ser Pathogenic/Likely pathogenic ★★ ⚠ same condition
ALG13 p.Asn511Ser Uncertain significance ★★ ⚠ same condition
ALG13 p.Lys335Gln Uncertain significance ★★ ⚠ same condition
ALG13 p.Tyr565Cys Uncertain significance ★★ ⚠ same condition
ALG13 c.2458-1G>A Uncertain significance ★★ same type
ALG13 c.2695+4G>A Uncertain significance ★★ same type
ALG13 c.2932+6T>C 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/alg13-p-cys265phe (accessed [today's date]).

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