Is ALG6 p.Met7Thr (c.20T>C) pathogenic?

ALG6 p.Met7Thr (c.20T>C) is classified Uncertain significance in ALG6 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-06). AlphaMissense: likely benign (0.1637); Very rare (popmax 8.5e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ALG6 p.Met7Thr (c.20T>C)?

ALG6 p.Met7Thr (c.20T>C) is associated with Inborn genetic diseases, ALG6-congenital disorder of glycosylation 1C (ClinVar).

How common is ALG6 p.Met7Thr (c.20T>C) in the general population?

ALG6 p.Met7Thr (c.20T>C) is very rare (popmax 8.5e-05%, nfe) (gnomAD).

What do computational predictors say about ALG6 p.Met7Thr (c.20T>C)?

AlphaMissense predicts likely benign (score 0.1637) — an in-silico prediction, not a clinical call.

ALG6 p.Met7Thr

c.20T>C · rs2523646252 · VCV1915590

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1637 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.5e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1637	likely benign
REVEL	0.261	benign-leaning
SaProt	LLR -7.79	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5	GERP 2.6, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 66 kb · p 0.00074 · regional, not allelic
Overall
CADD	18.52	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.5e-05% European (non-Finnish) · 1/1,175,888 alleles

Overall 6.86e-05% 1/1,457,236 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: ALG6
Protein: p.Met7Thr
Coding: c.20T>C
MANE Select: NM_013339
dbSNP: rs2523646252
Type: single nucleotide variant
Location: chr1:63370997 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: ALG6-congenital disorder of glycosylation 1C

Similar variants

ALG6 p.Met7Val Uncertain significance ★ ⚠ 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-met7thr (accessed [today's date]).

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