Is ALG6 p.Trp176Ser (c.527G>C) pathogenic?

ALG6 p.Trp176Ser (c.527G>C) is classified Uncertain significance in ALG6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-30). AlphaMissense: ambiguous (0.526); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ALG6 p.Trp176Ser (c.527G>C)?

ALG6 p.Trp176Ser (c.527G>C) is associated with Inborn genetic diseases (ClinVar).

How common is ALG6 p.Trp176Ser (c.527G>C) in the general population?

ALG6 p.Trp176Ser (c.527G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ALG6 p.Trp176Ser (c.527G>C)?

AlphaMissense predicts ambiguous (score 0.526) — an in-silico prediction, not a clinical call.

ALG6 p.Trp176Ser

c.527G>C · VCV4575089

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.526 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.526	ambiguous
REVEL	0.799	moderately pathogenic-leaning
SaProt	LLR -10.72	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 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 66 kb · p 0.00074 · regional, not allelic
Overall
CADD	29.3	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

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: ALG6
Protein: p.Trp176Ser
Coding: c.527G>C
MANE Select: NM_013339
Type: single nucleotide variant
Location: chr1:63411178 (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

Similar variants

ALG6 p.Trp176Ter Pathogenic ★ same residue
ALG6 p.Trp176Leu Likely benign ★ same residue
ALG6 p.Cys212Gly Uncertain significance ★★ ⚠ same condition
ALG6 p.Cys431Gly Uncertain significance ★★ ⚠ same condition
ALG6 p.Gly172Asp Uncertain significance ★★ ⚠ same condition
ALG6 p.Gly177Ser Uncertain significance ★★ ⚠ same condition
ALG6 p.Ile197Met Uncertain significance ★★ ⚠ same condition
ALG6 p.Met7Thr 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/alg6-p-trp176ser (accessed [today's date]).

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