Is ALG10 p.Ile454Leu (c.1360A>C) pathogenic?

ALG10 p.Ile454Leu (c.1360A>C) is classified Likely benign in ALG10 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-16). AlphaMissense: likely benign (0.0509); Absent from gnomAD v4.1.

How common is ALG10 p.Ile454Leu (c.1360A>C) in the general population?

ALG10 p.Ile454Leu (c.1360A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ALG10 p.Ile454Leu (c.1360A>C)?

AlphaMissense predicts likely benign (score 0.0509) — an in-silico prediction, not a clinical call.

ALG10 p.Ile454Leu

c.1360A>C · VCV3283952

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0509 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0509	likely benign
REVEL	0.022	moderately benign-leaning
SaProt	LLR -5.45	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 0.31	GERP -0.48, phastCons 0.36
Regional constraint	o/e 0.89	unconstrained · MANE · 4,312 bp · p 0.0095 · regional, not allelic
Overall
CADD	0.025	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: ALG10
Protein: p.Ile454Leu
Coding: c.1360A>C
MANE Select: NM_032834
Type: single nucleotide variant
Location: chr12:34026853 (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

Similar variants

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
ALG10 p.Ala125Thr 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-ile454leu (accessed [today's date]).

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