Is ALG6 p.Phe306Ile (c.916T>A) pathogenic?

ALG6 p.Phe306Ile (c.916T>A) is classified Uncertain significance in ALG6 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-08). AlphaMissense: likely benign (0.0701); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ALG6 p.Phe306Ile (c.916T>A)?

ALG6 p.Phe306Ile (c.916T>A) is associated with Inborn genetic diseases (ClinVar).

How common is ALG6 p.Phe306Ile (c.916T>A) in the general population?

ALG6 p.Phe306Ile (c.916T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ALG6 p.Phe306Ile (c.916T>A)?

AlphaMissense predicts likely benign (score 0.0701) — an in-silico prediction, not a clinical call.

ALG6 p.Phe306Ile

c.916T>A · rs769417698 · VCV2305536

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0701 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0701	likely benign
REVEL	0.249	benign-leaning
SaProt	LLR -6.29	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 0.94	GERP 1.8, phastCons 0.78
Regional constraint	o/e 0.86	unconstrained · MANE · 66 kb · p 0.00074 · regional, not allelic
Overall
CADD	17.01	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

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.Phe306Ile
Coding: c.916T>A
MANE Select: NM_013339
dbSNP: rs769417698
Type: single nucleotide variant
Location: chr1:63415886 (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.Phe306Val Uncertain significance ★ ⚠ 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
ALG6 p.Thr374Ala 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-phe306ile (accessed [today's date]).

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