Is ALG10 p.Leu456= (c.1366C>T) pathogenic?

ALG10 p.Leu456= (c.1366C>T) is classified Likely benign in ALG10 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-09-17). Very rare (popmax 0.00941%, nfe); Associated with ALG10-related disorder.

What condition is associated with ALG10 p.Leu456= (c.1366C>T)?

ALG10 p.Leu456= (c.1366C>T) is associated with ALG10-related disorder (ClinVar).

How common is ALG10 p.Leu456= (c.1366C>T) in the general population?

ALG10 p.Leu456= (c.1366C>T) is very rare (popmax 0.00941%, nfe) (gnomAD).

ALG10 p.Leu456=

c.1366C>T · rs1377334596 · VCV3040080

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00941%, nfe)

Conditions

ALG10-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.55	GERP 2.5, phastCons 0.8
Overall
CADD	5.734	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00941% European (non-Finnish) · 111/1,179,770 alleles

Filtering AF 0.00791% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00744%

Overall 0.00688% 111/1,613,532 alleles · very rare

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: ALG10
Protein: p.Leu456=
Coding: c.1366C>T
MANE Select: NM_032834
dbSNP: rs1377334596
Type: single nucleotide variant
Location: chr12:34026859 (GRCh38)
Gene constraint: LOEUF 0.901 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.51

Full ALG10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ALG10-related disorder

Similar variants

ALG10 p.Val118= Likely benign same condition
ALG10 p.Ser243= Benign ★★ same type
ALG10 p.Thr134= Benign ★★ same type
ALG10 p.Val269Ile Benign ★★ same type
ALG10 c.369+1G>T Likely pathogenic ★ same type
ALG10 p.Met61Val Likely pathogenic ★ ⚠ same type
ALG10 p.Ala11Asp Uncertain significance ★ ⚠ same type
ALG10 p.Ala11Thr 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/alg10-p-leu456 (accessed [today's date]).

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