Is CLN6 p.Phe261Ser (c.782T>C) pathogenic?

CLN6 p.Phe261Ser (c.782T>C) is classified Likely pathogenic in CLN6 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-06-24). AlphaMissense: likely pathogenic (0.9938); Absent from gnomAD v4.1; Associated with neurodevelopmental disorder.

What condition is associated with CLN6 p.Phe261Ser (c.782T>C)?

CLN6 p.Phe261Ser (c.782T>C) is associated with neurodevelopmental disorder (ClinVar).

How common is CLN6 p.Phe261Ser (c.782T>C) in the general population?

CLN6 p.Phe261Ser (c.782T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CLN6 p.Phe261Ser (c.782T>C)?

AlphaMissense predicts likely pathogenic (score 0.9938) — an in-silico prediction, not a clinical call.

CLN6 p.Phe261Ser

c.782T>C · rs2141136011 · VCV1064768

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9938 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

neurodevelopmental disorder

Computational evidence

Protein change
AlphaMissense	0.9938	likely pathogenic ✓ concordant with ClinVar · top 3% in CLN6
REVEL	0.895	moderately pathogenic-leaning
SaProt	LLR -9.87	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, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 21 kb · p 0.14 · regional, not allelic
Overall
CADD	28.1	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: CLN6
Protein: p.Phe261Ser
Coding: c.782T>C
MANE Select: NM_017882
dbSNP: rs2141136011
Type: single nucleotide variant
Location: chr15:68208294 (GRCh38)
Gene constraint: LOEUF 1.015 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.86

Full CLN6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

neurodevelopmental disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CLN6 p.Phe261Leu Uncertain significance ★ ⚠ same residue
CLN6 p.Phe261= Likely benign ★ same residue
CLN6 p.Val273Ala Likely pathogenic ★ ⚠ same condition
CLN6 c.297+1G>A Pathogenic/Likely pathogenic ★★ same type
CLN6 c.486+1G>A Likely pathogenic ★★ same type
CLN6 c.543-1G>A Likely pathogenic ★★ same type
CLN6 c.665+1G>A Pathogenic/Likely pathogenic ★★ same type
CLN6 c.665+1G>T Likely pathogenic ★★ 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/cln6-p-phe261ser (accessed [today's date]).

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