Is ALG14 p.Ile133Phe (c.397A>T) pathogenic?

ALG14 p.Ile133Phe (c.397A>T) is classified Uncertain significance in ALG14 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-13). AlphaMissense: ambiguous (0.413); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ALG14 p.Ile133Phe (c.397A>T)?

ALG14 p.Ile133Phe (c.397A>T) is associated with Inborn genetic diseases (ClinVar).

How common is ALG14 p.Ile133Phe (c.397A>T) in the general population?

ALG14 p.Ile133Phe (c.397A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ALG14 p.Ile133Phe (c.397A>T)?

AlphaMissense predicts ambiguous (score 0.413) — an in-silico prediction, not a clinical call.

ALG14 p.Ile133Phe

c.397A>T · VCV4037989

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.413 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.413	ambiguous
REVEL	0.185	benign-leaning
SaProt	LLR -10.61	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.43	GERP -3.8, phastCons 0.22
Regional constraint	o/e 1.06	unconstrained · MANE · 90 kb · p 0.32 · regional, not allelic
Overall
CADD	14.05	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: ALG14
Protein: p.Ile133Phe
Coding: c.397A>T
MANE Select: NM_144988
Type: single nucleotide variant
Location: chr1:95027152 (GRCh38)
Gene constraint: LOEUF 1.055 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.06
Residue 133: a UniProt-annotated variant site (in cms15)

Full ALG14 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

ALG14 p.Arg104Gln Uncertain significance ★★ ⚠ same condition
ALG14 p.Arg109Trp Uncertain significance ★★ ⚠ same condition
ALG14 p.Asn82Ser Uncertain significance ★★ ⚠ same condition
ALG14 p.Glu110Lys Uncertain significance ★★ same condition
ALG14 p.His190Gln Uncertain significance ★★ ⚠ same condition
ALG14 p.Pro200Leu Uncertain significance ★★ ⚠ same condition
ALG14 p.Ser209Leu Uncertain significance ★★ ⚠ same condition
ALG14 p.Val136Met 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/alg14-p-ile133phe (accessed [today's date]).

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