Is ALG12 p.Pro438Ser (c.1312C>T) pathogenic?

ALG12 p.Pro438Ser (c.1312C>T) is classified Uncertain significance in ALG12 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-12). AlphaMissense: likely benign (0.0739); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ALG12 p.Pro438Ser (c.1312C>T)?

ALG12 p.Pro438Ser (c.1312C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ALG12 p.Pro438Ser (c.1312C>T) in the general population?

ALG12 p.Pro438Ser (c.1312C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ALG12 p.Pro438Ser (c.1312C>T)?

AlphaMissense predicts likely benign (score 0.0739) — an in-silico prediction, not a clinical call.

ALG12 p.Pro438Ser

c.1312C>T · VCV3284080

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0739 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0739	likely benign
REVEL	0.263	benign-leaning
SaProt	LLR -11.27	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.3	GERP 1.6, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 9,924 bp · p 0.17 · regional, not allelic
Overall
CADD	17.9	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: ALG12
Protein: p.Pro438Ser
Coding: c.1312C>T
MANE Select: NM_024105
Type: single nucleotide variant
Location: chr22:49903993 (GRCh38)
Gene constraint: LOEUF 0.965 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.26
Residue 438: a UniProt-annotated variant site (in cdg1g)

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.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
ALG12 p.Arg120Trp Uncertain significance ★★ ⚠ same condition
ALG12 p.Arg202Gln 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-pro438ser (accessed [today's date]).

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