Is ALG13 p.Leu306Val (c.916C>G) pathogenic?

ALG13 p.Leu306Val (c.916C>G) is classified Uncertain significance in ALG13 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-07-10). AlphaMissense: likely pathogenic (0.5905); Very rare (popmax 0.00228%, amr); Associated with Inborn genetic diseases.

What condition is associated with ALG13 p.Leu306Val (c.916C>G)?

ALG13 p.Leu306Val (c.916C>G) is associated with Inborn genetic diseases (ClinVar).

How common is ALG13 p.Leu306Val (c.916C>G) in the general population?

ALG13 p.Leu306Val (c.916C>G) is very rare (popmax 0.00228%, amr) (gnomAD).

What do computational predictors say about ALG13 p.Leu306Val (c.916C>G)?

AlphaMissense predicts likely pathogenic (score 0.5905) — an in-silico prediction, not a clinical call.

ALG13 p.Leu306Val

c.916C>G · rs1248942119 · VCV985537

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5905 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00228%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5905	likely pathogenic
REVEL	0.385	indeterminate
SaProt	LLR -11.27	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 5.4, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 8,848 bp · p 0.46 · regional, not allelic
Overall
CADD	24.2	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

Grpmax group 0.00228% Admixed American · 1/43,896 alleles

Overall 8.51e-05% 1/1,174,487 alleles · very rare exomes 1/1,061,159 · genomes 0/113,328 · joint denominator

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.Leu306Val
Coding: c.916C>G
MANE Select: NM_001099922
dbSNP: rs1248942119
Type: single nucleotide variant
Location: chrX:111712514 (GRCh38)
Structure: AlphaFold pLDDT 54.42
Residue 306: the otu domain; the 'deubiquitinase activity' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ALG13 p.Leu306= Likely benign ★ same residue
ALG13 p.Ala540Val Uncertain significance ★★ ⚠ same condition
ALG13 p.Arg290Gln Uncertain significance ★★ ⚠ same condition
ALG13 p.Arg318Cys Uncertain significance ★★ ⚠ same condition
ALG13 p.Asn218Asp Uncertain significance ★★ ⚠ same condition
ALG13 p.Gly570Glu Uncertain significance ★★ ⚠ same condition
ALG13 p.Lys68Thr Uncertain significance ★★ ⚠ same condition
ALG13 p.Ser66Tyr Uncertain significance ★★ ⚠ same condition

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-leu306val (accessed [today's date]).

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