Is ALG12 p.Pro384Leu (c.1151C>T) pathogenic?

ALG12 p.Pro384Leu (c.1151C>T) is classified Uncertain significance in ALG12 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-07). AlphaMissense: likely benign (0.0796); Very rare (popmax 6.84e-05%); Associated with Inborn genetic diseases.

What condition is associated with ALG12 p.Pro384Leu (c.1151C>T)?

ALG12 p.Pro384Leu (c.1151C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ALG12 p.Pro384Leu (c.1151C>T) in the general population?

ALG12 p.Pro384Leu (c.1151C>T) is very rare (popmax 6.84e-05%) (gnomAD).

What do computational predictors say about ALG12 p.Pro384Leu (c.1151C>T)?

AlphaMissense predicts likely benign (score 0.0796) — an in-silico prediction, not a clinical call.

ALG12 p.Pro384Leu

c.1151C>T · VCV4037936

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0796 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.84e-05%)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0796	likely benign
REVEL	0.298	indeterminate
SaProt	LLR -11.71	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 11	GERP 1.5, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 9,924 bp · p 0.17 · regional, not allelic
Overall
CADD	24.8	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

Grpmax group 6.84e-05%

Overall 6.84e-05% 1/1,461,880 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: ALG12
Protein: p.Pro384Leu
Coding: c.1151C>T
MANE Select: NM_024105
Type: single nucleotide variant
Location: chr22:49904348 (GRCh38)
Gene constraint: LOEUF 0.965 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.26

Full ALG12 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

ALG12 p.Pro384Ser Uncertain significance ★ ⚠ same residue
ALG12 p.Pro384= Likely benign ★ same residue
ALG12 p.Ala135Thr Uncertain significance ★★ ⚠ same condition
ALG12 p.Ala290Thr Uncertain significance ★★ ⚠ same condition
ALG12 p.Ala300Thr Uncertain significance ★★ ⚠ same condition
ALG12 p.Ala357Thr Uncertain significance ★★ ⚠ same condition
ALG12 p.Ala411Thr Uncertain significance ★★ ⚠ same condition
ALG12 p.Arg10Trp 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/alg12-p-pro384leu (accessed [today's date]).

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