Is CHRND p.Ser289Phe (c.866C>T) pathogenic?

CHRND p.Ser289Phe (c.866C>T) is classified Likely pathogenic in CHRND (ClinVar, Single submitter, 2 submitters; last evaluated 2024-03-24). AlphaMissense: likely pathogenic (0.8387); Absent from gnomAD v4.1; Associated with lethal multiple pterygium syndrome.

What condition is associated with CHRND p.Ser289Phe (c.866C>T)?

CHRND p.Ser289Phe (c.866C>T) is associated with lethal multiple pterygium syndrome, congenital myasthenic syndrome 3A (ClinVar).

How common is CHRND p.Ser289Phe (c.866C>T) in the general population?

CHRND p.Ser289Phe (c.866C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHRND p.Ser289Phe (c.866C>T)?

AlphaMissense predicts likely pathogenic (score 0.8387) — an in-silico prediction, not a clinical call.

CHRND p.Ser289Phe

c.866C>T · rs121909502 · VCV18363

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8387 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

lethal multiple pterygium syndrome

Computational evidence

Protein change
AlphaMissense	0.8387	likely pathogenic ✓ concordant with ClinVar
REVEL	0.87	moderately pathogenic-leaning
SaProt	LLR -8.35	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 7.5	GERP 2.2, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 9,093 bp · p 0.12 · 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

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: CHRND
Protein: p.Ser289Phe
Coding: c.866C>T
MANE Select: NM_000751
dbSNP: rs121909502
Type: single nucleotide variant
Location: chr2:232531397 (GRCh38)
Gene constraint: LOEUF 0.848 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.21 · 25 PDB
Residue 289: a UniProt-annotated variant site (in cms3a; delayed closure of achr ion channels, increasing the propensity for open-channel block, as well as a reduced rate of channel opening); an α-helix

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

Disease context

lethal multiple pterygium syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: congenital myasthenic syndrome 3A

Similar variants

CHRND c.1252+1G>A Pathogenic/Likely pathogenic ★★ same condition
CHRND c.821-2A>C Pathogenic/Likely pathogenic ★★ same condition
CHRND c.933-2A>G Likely pathogenic ★★ same condition
CHRND p.Arg336Gln Likely pathogenic ★★ same condition
CHRND p.Arg43Trp Pathogenic/Likely pathogenic ★★ same condition
CHRND p.Cys257Arg Pathogenic/Likely pathogenic ★★ same condition
CHRND p.Trp78Ter Pathogenic ★★ same condition
CHRND p.Trp83Ter 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/chrnd-p-ser289phe (accessed [today's date]).

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