Is ALG12 p.Ala267Val (c.800C>T) pathogenic?

ALG12 p.Ala267Val (c.800C>T) is classified Uncertain significance in ALG12 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-12). AlphaMissense: likely benign (0.1734); Very rare (popmax 0.00329%, sas); Associated with ALG12-congenital disorder of glycosylation.

What condition is associated with ALG12 p.Ala267Val (c.800C>T)?

ALG12 p.Ala267Val (c.800C>T) is associated with ALG12-congenital disorder of glycosylation (ClinVar).

How common is ALG12 p.Ala267Val (c.800C>T) in the general population?

ALG12 p.Ala267Val (c.800C>T) is very rare (popmax 0.00329%, sas) (gnomAD).

How is ALG12-CDG inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about ALG12 p.Ala267Val (c.800C>T)?

AlphaMissense predicts likely benign (score 0.1734) — an in-silico prediction, not a clinical call.

ALG12 p.Ala267Val

c.800C>T · rs1287436259 · VCV1510779

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1734 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

ALG12-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.1734	likely benign
REVEL	0.589	indeterminate
SaProt	LLR -11.77	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP 9.6	GERP 1.6, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 9,924 bp · p 0.17 · regional, not allelic
Overall
CADD	29.5	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 0.00329% South Asian · 3/91,074 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000205% 3/1,460,992 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.Ala267Val
Coding: c.800C>T
MANE Select: NM_024105
dbSNP: rs1287436259
Type: single nucleotide variant
Location: chr22:49907913 (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

ALG12-congenital disorder of glycosylation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For ALG12-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

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ALG12 p.Arg202Ter Pathogenic/Likely pathogenic ★★ same condition
ALG12 p.Gly101Arg Likely pathogenic ★★ same condition
ALG12 p.Thr67Met Pathogenic/Likely pathogenic ★★ same condition
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ALG12 c.470-3C>T 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-ala267val (accessed [today's date]).

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