Is CLN5 p.Ala72Val (c.215C>T) pathogenic?

CLN5 p.Ala72Val (c.215C>T) is classified Uncertain significance in CLN5 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-27). AlphaMissense: likely pathogenic (0.8636); Absent from gnomAD v4.1; Associated with neuronal ceroid lipofuscinosis.

What condition is associated with CLN5 p.Ala72Val (c.215C>T)?

CLN5 p.Ala72Val (c.215C>T) is associated with neuronal ceroid lipofuscinosis (ClinVar).

How common is CLN5 p.Ala72Val (c.215C>T) in the general population?

CLN5 p.Ala72Val (c.215C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CLN5 p.Ala72Val (c.215C>T)?

AlphaMissense predicts likely pathogenic (score 0.8636) — an in-silico prediction, not a clinical call.

CLN5 p.Ala72Val

c.215C>T · rs2154034628 · VCV1371554

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8636 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

neuronal ceroid lipofuscinosis

Computational evidence

Protein change
AlphaMissense	0.8636	likely pathogenic
REVEL	0.764	pathogenic-leaning
SaProt	LLR -5.23	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.96 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6	GERP 2.7, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 8,867 bp · p 0.55 · regional, not allelic
Overall
CADD	27.8	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: CLN5
Protein: p.Ala72Val
Coding: c.215C>T
MANE Select: NM_006493
dbSNP: rs2154034628
Type: single nucleotide variant
Location: chr13:76995104 (GRCh38)
Gene constraint: LOEUF 1.197 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.05 · 1 PDB
Residue 72: a disulfide bond

Full CLN5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

neuronal ceroid lipofuscinosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CLN5 p.Ala72Gly Uncertain significance ★ ⚠ same residue
CLN5 c.174-2A>G Likely pathogenic ★★ same condition
CLN5 p.Arg150Ter Pathogenic ★★ same condition
CLN5 p.Arg63His Pathogenic/Likely pathogenic ★★ ⚠ same condition
CLN5 p.Arg96Ter Pathogenic/Likely pathogenic ★★ same condition
CLN5 p.Asn143Ser Pathogenic/Likely pathogenic ★★ ⚠ same condition
CLN5 p.Cys77Tyr Likely pathogenic ★★ ⚠ same condition
CLN5 p.Gln183Ter Pathogenic/Likely pathogenic ★★ 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/cln5-p-ala72val (accessed [today's date]).

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