Is CNP p.Ser82Leu (c.245C>T) pathogenic?

CNP p.Ser82Leu (c.245C>T) is classified Pathogenic in CNP (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-11-10). AlphaMissense: ambiguous (0.4313); Absent from gnomAD v4.1; Associated with leukodystrophy, hypomyelinating, 20.

What condition is associated with CNP p.Ser82Leu (c.245C>T)?

CNP p.Ser82Leu (c.245C>T) is associated with leukodystrophy, hypomyelinating, 20 (ClinVar).

How common is CNP p.Ser82Leu (c.245C>T) in the general population?

CNP p.Ser82Leu (c.245C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CNP p.Ser82Leu (c.245C>T)?

AlphaMissense predicts ambiguous (score 0.4313) — an in-silico prediction, not a clinical call.

CNP p.Ser82Leu

c.245C>T · rs2050933471 · VCV983536

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4313 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

leukodystrophy, hypomyelinating, 20

Computational evidence

Protein change
AlphaMissense	0.4313	ambiguous
REVEL	0.291	indeterminate
SaProt	LLR -14.60	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.64	unconstrained · MANE · 1,784 bp · p 6.9e-09 · regional, not allelic
Overall
CADD	26.5	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: CNP
Protein: p.Ser82Leu
Coding: c.245C>T
MANE Select: NM_033133
dbSNP: rs2050933471
Type: single nucleotide variant
Location: chr17:41968309 (GRCh38)
Gene constraint: LOEUF 0.379 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 87.54 · 1 PDB
Residue 82: a UniProt-annotated variant site (in hld20; uncertain significance; decreased protein levels in patient cells)

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

Disease context

leukodystrophy, hypomyelinating, 20 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CNP p.Ala281Val Uncertain significance ★ ⚠ same condition
CNP p.Gln306His Uncertain significance ★ same condition
CNP p.Arg353Trp Uncertain significance ★★ ⚠ same type
CNP p.Gly365= Benign ★★ same type
CNP p.Ala218Val Uncertain significance ★ ⚠ same type
CNP p.Ala269Val Uncertain significance ★ ⚠ same type
CNP p.Ala92Thr Uncertain significance ★ ⚠ same type
CNP p.Arg114Gln 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/cnp-p-ser82leu (accessed [today's date]).

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