Is ALG2 p.Thr316Pro (c.946A>C) pathogenic?

ALG2 p.Thr316Pro (c.946A>C) is classified Uncertain significance in ALG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-01). AlphaMissense: likely benign (0.211); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ALG2 p.Thr316Pro (c.946A>C)?

ALG2 p.Thr316Pro (c.946A>C) is associated with Inborn genetic diseases (ClinVar).

How common is ALG2 p.Thr316Pro (c.946A>C) in the general population?

ALG2 p.Thr316Pro (c.946A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ALG2 p.Thr316Pro (c.946A>C)?

AlphaMissense predicts likely benign (score 0.211) — an in-silico prediction, not a clinical call.

ALG2 p.Thr316Pro

c.946A>C · VCV4038129

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.211 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.211	likely benign
REVEL	0.475	indeterminate
SaProt	LLR -10.73	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP 1.5, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 3,957 bp · p 0.038 · regional, not allelic
Overall
CADD	20.3	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: ALG2
Protein: p.Thr316Pro
Coding: c.946A>C
MANE Select: NM_033087
Type: single nucleotide variant
Location: chr9:99218239 (GRCh38)
Gene constraint: LOEUF 1.408 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 91.03

Full ALG2 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

ALG2 p.Thr316Met Uncertain significance ★ ⚠ same residue
ALG2 p.Thr316= Likely benign ★ same residue
ALG2 p.Ala71Gly Uncertain significance ★★ ⚠ same condition
ALG2 p.Arg393Gly Uncertain significance ★★ ⚠ same condition
ALG2 p.Arg7Trp Uncertain significance ★★ ⚠ same condition
ALG2 p.Asp148Gly Uncertain significance ★★ ⚠ same condition
ALG2 p.Cys120Tyr Uncertain significance ★★ ⚠ same condition
ALG2 p.Gln338His 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/alg2-p-thr316pro (accessed [today's date]).

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