Is ALG6 p.Met202Val (c.604A>G) pathogenic?

ALG6 p.Met202Val (c.604A>G) is classified Uncertain significance in ALG6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-24). AlphaMissense: ambiguous (0.4841); Very rare (popmax 0.0011%, sas); Associated with ALG6-congenital disorder of glycosylation 1C.

What condition is associated with ALG6 p.Met202Val (c.604A>G)?

ALG6 p.Met202Val (c.604A>G) is associated with ALG6-congenital disorder of glycosylation 1C (ClinVar).

How common is ALG6 p.Met202Val (c.604A>G) in the general population?

ALG6 p.Met202Val (c.604A>G) is very rare (popmax 0.0011%, sas) (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.Met202Val (c.604A>G)?

AlphaMissense predicts ambiguous (score 0.4841) — an in-silico prediction, not a clinical call.

ALG6 p.Met202Val

c.604A>G · rs757012140 · VCV2193051

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4841 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

ALG6-congenital disorder of glycosylation 1C

Computational evidence

Protein change
AlphaMissense	0.4841	ambiguous
REVEL	0.942	strongly pathogenic-leaning
SaProt	LLR -12.77	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.1, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 66 kb · p 0.00074 · regional, not allelic
Overall
CADD	24.3	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 0.0011% South Asian · 1/91,090 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000496% 8/1,613,884 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,476
South Asiangrpmax	0.0011%	91,090
European (non-Finnish)	0.000509%	196,655

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Met202Val
Coding: c.604A>G
MANE Select: NM_013339
dbSNP: rs757012140
Type: single nucleotide variant
Location: chr1:63411255 (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.Met202Leu 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-met202val (accessed [today's date]).

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