Is CLN3 p.Ala388Val (c.1163C>T) pathogenic?

CLN3 p.Ala388Val (c.1163C>T) is classified Uncertain significance in CLN3 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2024-11-11). AlphaMissense: ambiguous (0.399); Ultra-rare (popmax 0.0413%, afr); Associated with Inborn genetic diseases.

What condition is associated with CLN3 p.Ala388Val (c.1163C>T)?

CLN3 p.Ala388Val (c.1163C>T) is associated with Inborn genetic diseases, neuronal ceroid lipofuscinosis 3, neuronal ceroid lipofuscinosis (ClinVar).

How common is CLN3 p.Ala388Val (c.1163C>T) in the general population?

CLN3 p.Ala388Val (c.1163C>T) is ultra-rare (popmax 0.0413%, afr) (gnomAD).

What do computational predictors say about CLN3 p.Ala388Val (c.1163C>T)?

AlphaMissense predicts ambiguous (score 0.399) — an in-silico prediction, not a clinical call.

CLN3 p.Ala388Val

c.1163C>T · rs148514847 · VCV194477

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

ambiguous

0.399 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0413%, afr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.399	ambiguous
REVEL	0.769	pathogenic-leaning
SaProt	LLR -8.34	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.2, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 14 kb · p 0.08 · regional, not allelic
Overall
CADD	26.4	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 0.0413% African / African-American · 31/75,040 alleles

Filtering AF 0.0298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.026%

Overall 0.00204% 33/1,614,132 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0413%	2,421
Admixed American	0.00167%	60,002
Remaining individualsnot grpmax-eligible	0.0016%	62,510

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: CLN3
Protein: p.Ala388Val
Coding: c.1163C>T
MANE Select: NM_001042432
dbSNP: rs148514847
Type: single nucleotide variant
Location: chr16:28477771 (GRCh38)
Gene constraint: LOEUF 1.022 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 81.81

Full CLN3 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

Also linked: neuronal ceroid lipofuscinosis 3 neuronal ceroid lipofuscinosis

Similar variants

CLN3 p.Ala388Thr Uncertain significance ★ ⚠ same residue
CLN3 p.Ala388= Likely benign ★ same residue
CLN3 c.1056+1G>A Likely pathogenic ★★ same condition
CLN3 c.1056+1G>T Likely pathogenic ★★ same condition
CLN3 c.1056+3A>C Pathogenic/Likely pathogenic ★★ same condition
CLN3 c.1197+1G>A Pathogenic/Likely pathogenic ★★ same condition
CLN3 c.1198-1G>T Pathogenic/Likely pathogenic ★★ same condition
CLN3 c.125+1G>C 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/cln3-p-ala388val (accessed [today's date]).

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