Is CHRND p.Ser274fs (c.822del) pathogenic?

CHRND p.Ser274fs (c.822del) is classified Likely pathogenic in CHRND (ClinVar, Single submitter, 1 submitter; last evaluated 2014-06-03). Very rare (popmax 8.49e-05%, nfe); Associated with ptosis.

What condition is associated with CHRND p.Ser274fs (c.822del)?

CHRND p.Ser274fs (c.822del) is associated with ptosis (ClinVar).

How common is CHRND p.Ser274fs (c.822del) in the general population?

CHRND p.Ser274fs (c.822del) is very rare (popmax 8.49e-05%, nfe) (gnomAD).

CHRND p.Ser274fs

c.822del · rs1057518958 · VCV374186

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.49e-05%, nfe)

Conditions

ptosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 8 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.49e-05% European (non-Finnish) · 1/1,178,318 alleles

Overall 6.85e-05% 1/1,459,716 alleles · very rare

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: CHRND
Protein: p.Ser274fs
Coding: c.822del
MANE Select: NM_000751
dbSNP: rs1057518958
Type: Deletion
Location: chr2:232531353 (GRCh38)
Gene constraint: LOEUF 0.848 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.21 · 25 PDB
Residue 274: an α-helix

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

Disease context

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

Similar variants

CHRND p.Ser274Arg Uncertain significance ★★ ⚠ same residue
CHRND p.Trp462Leu Likely pathogenic ★ same condition
CHRND p.Ser370fs Pathogenic/Likely pathogenic ★★ same type
CHRND p.Asn456fs Uncertain significance ★★ same type
CHRND c.820_820+1del Pathogenic ★ same type
CHRND p.Ala13fs Pathogenic ★ same type
CHRND p.Ala427fs Likely pathogenic ★ same type
CHRND p.Arg30fs 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/chrnd-p-ser274fs (accessed [today's date]).

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