Is ALG5 p.Gln235Leu (c.704A>T) pathogenic?

ALG5 p.Gln235Leu (c.704A>T) is classified Uncertain significance in ALG5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-03). AlphaMissense: likely pathogenic (0.9015); Absent from gnomAD v4.1; Associated with polycystic kidney disease 7.

What condition is associated with ALG5 p.Gln235Leu (c.704A>T)?

ALG5 p.Gln235Leu (c.704A>T) is associated with polycystic kidney disease 7 (ClinVar).

How common is ALG5 p.Gln235Leu (c.704A>T) in the general population?

ALG5 p.Gln235Leu (c.704A>T) is absent from gnomAD v4.1 (gnomAD).

How is Autosomal dominant polycystic kidney disease inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about ALG5 p.Gln235Leu (c.704A>T)?

AlphaMissense predicts likely pathogenic (score 0.9015) — an in-silico prediction, not a clinical call.

ALG5 p.Gln235Leu

c.704A>T · VCV3764803

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9015 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

polycystic kidney disease 7

Computational evidence

Protein change
AlphaMissense	0.9015	likely pathogenic
REVEL	0.697	pathogenic-leaning
SaProt	LLR -14.12	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.1, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 49 kb · p 9.9e-06 · regional, not allelic
Overall
CADD	29.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: ALG5
Protein: p.Gln235Leu
Coding: c.704A>T
MANE Select: NM_013338
Type: single nucleotide variant
Location: chr13:36965644 (GRCh38)
Gene constraint: LOEUF 0.823 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 92.29

Full ALG5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

polycystic kidney disease 7 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal dominant polycystic kidney disease (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

ALG5 p.Gln235His Uncertain significance ★ ⚠ same residue
ALG5 p.Gln235fs Pathogenic same residue
ALG5 p.Thr249Met Uncertain significance ★★ ⚠ same condition
ALG5 c.239-2A>G Likely pathogenic ★ same condition
ALG5 p.Arg39Ter Likely pathogenic ★ same condition
ALG5 p.Arg97Ter Pathogenic ★ same condition
ALG5 p.Trp224Ter Likely pathogenic ★ same condition
ALG5 p.Arg309Ter 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/alg5-p-gln235leu (accessed [today's date]).

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