Is ALG14 p.Ile52Asn (c.155T>A) pathogenic?

ALG14 p.Ile52Asn (c.155T>A) is classified Uncertain significance in ALG14 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-07-24). AlphaMissense: likely pathogenic (0.84); Very rare (popmax 8.48e-05%, nfe); Associated with ALG14-related disorder.

What condition is associated with ALG14 p.Ile52Asn (c.155T>A)?

ALG14 p.Ile52Asn (c.155T>A) is associated with ALG14-related disorder (ClinVar).

How common is ALG14 p.Ile52Asn (c.155T>A) in the general population?

ALG14 p.Ile52Asn (c.155T>A) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about ALG14 p.Ile52Asn (c.155T>A)?

AlphaMissense predicts likely pathogenic (score 0.84) — an in-silico prediction, not a clinical call.

ALG14 p.Ile52Asn

c.155T>A · rs2525848272 · VCV3030136

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.84 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ALG14-related disorder

Computational evidence

Protein change
AlphaMissense	0.84	likely pathogenic
REVEL	0.834	moderately pathogenic-leaning
SaProt	LLR -8.58	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.4, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 90 kb · p 0.32 · regional, not allelic
Overall
CADD	28.4	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 8.48e-05% European (non-Finnish) · 1/1,179,612 alleles

Overall 6.84e-05% 1/1,461,118 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: ALG14
Protein: p.Ile52Asn
Coding: c.155T>A
MANE Select: NM_144988
dbSNP: rs2525848272
Type: single nucleotide variant
Location: chr1:95064999 (GRCh38)
Gene constraint: LOEUF 1.055 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.06

Full ALG14 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ALG14-related disorder

Similar variants

ALG14 p.Ile102Asn Uncertain significance ⚠ same condition
ALG14 c.289-8631T>C Likely benign same condition
ALG14 p.Ala13Ser Uncertain significance ★★ ⚠ same type
ALG14 p.Arg104Gln Uncertain significance ★★ ⚠ same type
ALG14 p.Arg109Gln Uncertain significance ★★ ⚠ same type
ALG14 p.Arg109Trp Uncertain significance ★★ ⚠ same type
ALG14 p.Asn61Asp Uncertain significance ★★ ⚠ same type
ALG14 p.Asn61Ser Uncertain significance ★★ ⚠ same type

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-ile52asn (accessed [today's date]).

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