Is ALG13 p.Val20Ala (c.59T>C) pathogenic?

ALG13 p.Val20Ala (c.59T>C) is classified Uncertain significance in ALG13 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-13). AlphaMissense: ambiguous (0.5353); Absent from gnomAD v4.1.

How common is ALG13 p.Val20Ala (c.59T>C) in the general population?

ALG13 p.Val20Ala (c.59T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ALG13 p.Val20Ala (c.59T>C)?

AlphaMissense predicts ambiguous (score 0.5353) — an in-silico prediction, not a clinical call.

ALG13 p.Val20Ala

c.59T>C · rs1057522579 · VCV386700

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5353 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.5353	ambiguous
REVEL	0.572	indeterminate
SaProt	LLR -9.83	tolerated
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.8	GERP 2, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 27 kb · p 0.23 · regional, not allelic
Overall
CADD	24.5	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.Val20Ala
Coding: c.59T>C
MANE Select: NM_001099922
dbSNP: rs1057522579
Type: single nucleotide variant
Location: chrX:111681277 (GRCh38)
Structure: AlphaFold pLDDT 54.42
Residue 20: the 'glycosyltransferase activity' region

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

Similar variants

ALG13 p.Val20= Likely benign ★ same residue
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

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-val20ala (accessed [today's date]).

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