Is ALG6 p.Pro32Leu (c.95C>T) pathogenic?

ALG6 p.Pro32Leu (c.95C>T) is classified Uncertain significance in ALG6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-24). AlphaMissense: likely benign (0.1359); Ultra-rare (popmax 0.0147%, afr); Associated with ALG6-congenital disorder of glycosylation 1C.

What condition is associated with ALG6 p.Pro32Leu (c.95C>T)?

ALG6 p.Pro32Leu (c.95C>T) is associated with ALG6-congenital disorder of glycosylation 1C (ClinVar).

How common is ALG6 p.Pro32Leu (c.95C>T) in the general population?

ALG6 p.Pro32Leu (c.95C>T) is ultra-rare (popmax 0.0147%, afr) (gnomAD).

How is ALG6-CDG inherited?

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

What do computational predictors say about ALG6 p.Pro32Leu (c.95C>T)?

AlphaMissense predicts likely benign (score 0.1359) — an in-silico prediction, not a clinical call.

ALG6 p.Pro32Leu

c.95C>T · rs770413804 · VCV1493494

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1359 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0147%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ALG6-congenital disorder of glycosylation 1C

Computational evidence

Protein change
AlphaMissense	0.1359	likely benign
REVEL	0.868	moderately pathogenic-leaning
SaProt	LLR -11.61	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2.7, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 66 kb · p 0.00074 · regional, not allelic
Overall
CADD	29.6	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 0.0147% African / African-American · 11/74,844 alleles

Filtering AF 0.00816% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00634%

Overall 0.00446% 72/1,613,676 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0147%	6,804
East Asian	0.00669%	14,954
Remaining individualsnot grpmax-eligible	0.0064%	15,620
Admixed American	0.005%	19,995
European (non-Finnish)	0.00415%	24,079
South Asian	0.0022%	45,534

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: ALG6
Protein: p.Pro32Leu
Coding: c.95C>T
MANE Select: NM_013339
dbSNP: rs770413804
Type: single nucleotide variant
Location: chr1:63396525 (GRCh38)
Gene constraint: LOEUF 0.892 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.08

Full ALG6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ALG6-congenital disorder of glycosylation 1C — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For ALG6-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

ALG6 p.Pro32= Likely benign ★★ same residue
ALG6 c.1128-1G>A Likely pathogenic ★★ same condition
ALG6 c.1128-2A>C Likely pathogenic ★★ same condition
ALG6 c.1326+1G>A Pathogenic/Likely pathogenic ★★ same condition
ALG6 c.257+5G>A Pathogenic/Likely pathogenic ★★ same condition
ALG6 c.429+1G>T Likely pathogenic ★★ same condition
ALG6 c.495-2A>G Likely pathogenic ★★ same condition
ALG6 c.495-2A>T Likely pathogenic ★★ 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/alg6-p-pro32leu (accessed [today's date]).

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