Is ALG13 p.Arg304Ser (c.912A>C) pathogenic?

ALG13 p.Arg304Ser (c.912A>C) is classified Uncertain significance in ALG13 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-01). AlphaMissense: ambiguous (0.5197); Absent from gnomAD v4.1.

How common is ALG13 p.Arg304Ser (c.912A>C) in the general population?

ALG13 p.Arg304Ser (c.912A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ALG13 p.Arg304Ser (c.912A>C)?

AlphaMissense predicts ambiguous (score 0.5197) — an in-silico prediction, not a clinical call.

ALG13 p.Arg304Ser

c.912A>C · rs1939940766 · VCV2661210

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5197 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.5197	ambiguous
REVEL	0.199	benign-leaning
SaProt	LLR -6.11	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 5.4, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 8,848 bp · p 0.46 · regional, not allelic
Overall
CADD	16.92	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: ALG13
Protein: p.Arg304Ser
Coding: c.912A>C
MANE Select: NM_001099922
dbSNP: rs1939940766
Type: single nucleotide variant
Location: chrX:111712510 (GRCh38)
Structure: AlphaFold pLDDT 54.42
Residue 304: the otu domain; the 'deubiquitinase activity' region

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

Similar variants

ALG13 p.Asn107Ser Pathogenic/Likely pathogenic ★★ ⚠ same type
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
ALG13 c.834+3A>G Uncertain significance ★★ same type
ALG13 c.932+2T>C Uncertain significance ★★ same type
ALG13 p.Ala1044Thr Uncertain significance ★★ ⚠ same type
ALG13 p.Ala173Val 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-arg304ser (accessed [today's date]).

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