Is ALG13 p.Val1013Ala (c.3038T>C) pathogenic?

ALG13 p.Val1013Ala (c.3038T>C) is classified Uncertain significance in ALG13 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-24). AlphaMissense: likely benign (0.083); Very rare (popmax 0.00218%, amr).

How common is ALG13 p.Val1013Ala (c.3038T>C) in the general population?

ALG13 p.Val1013Ala (c.3038T>C) is very rare (popmax 0.00218%, amr) (gnomAD).

What do computational predictors say about ALG13 p.Val1013Ala (c.3038T>C)?

AlphaMissense predicts likely benign (score 0.083) — an in-silico prediction, not a clinical call.

ALG13 p.Val1013Ala

c.3038T>C · VCV3368370

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.083 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00218%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.083	likely benign
REVEL	0.028	moderately benign-leaning
SaProt	LLR -5.96	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 0.68	GERP -3.8, phastCons 0.032
Regional constraint	o/e 1.05	unconstrained · MANE · 2,374 bp · p 0.62 · regional, not allelic
Overall
CADD	5.255	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

Grpmax group 0.00218% Admixed American · 1/45,790 alleles

Overall 0.000165% 2/1,209,239 alleles · very rare exomes 2/1,096,133 · genomes 0/113,106 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00218%	45,790
European (non-Finnish)	0.000112%	893,903

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ALG13
Protein: p.Val1013Ala
Coding: c.3038T>C
MANE Select: NM_001099922
Type: single nucleotide variant
Location: chrX:111757652 (GRCh38)
Structure: AlphaFold pLDDT 54.42

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

Similar variants

ALG13 p.Val1013= Benign/Likely benign ★★ same residue
ALG13 p.Val1013Ile Uncertain significance ★ ⚠ same residue
ALG13 p.Val1013Glu 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

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-val1013ala (accessed [today's date]).

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