Is CHRND p.Phe160= (c.480C>T) pathogenic?

CHRND p.Phe160= (c.480C>T) is classified Conflicting classifications of pathogenicity in CHRND (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-10-31). Ultra-rare (popmax 0.0178%, eas); Associated with lethal multiple pterygium syndrome.

What condition is associated with CHRND p.Phe160= (c.480C>T)?

CHRND p.Phe160= (c.480C>T) is associated with lethal multiple pterygium syndrome, congenital myasthenic syndrome (ClinVar).

How common is CHRND p.Phe160= (c.480C>T) in the general population?

CHRND p.Phe160= (c.480C>T) is ultra-rare (popmax 0.0178%, eas) (gnomAD).

CHRND p.Phe160=

c.480C>T · rs200986300 · VCV714461

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0178%, eas)

Conditions

lethal multiple pterygium syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.28	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6	GERP -4.3
Overall
CADD	12.06	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0178% East Asian · 8/44,880 alleles

Filtering AF 0.00884% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00641%

Overall 0.00242% 39/1,614,134 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0178%	5,610
Remaining individualsnot grpmax-eligible	0.0144%	6,946
African / African-American	0.012%	8,339
South Asian	0.0011%	91,066
European (non-Finnish)	0.00102%	98,337

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.Phe160=
Coding: c.480C>T
MANE Select: NM_000751
dbSNP: rs200986300
Type: single nucleotide variant
Location: chr2:232528627 (GRCh38)
Gene constraint: LOEUF 0.848 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.21 · 25 PDB
Residue 160: a disulfide bond

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

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-phe160 (accessed [today's date]).

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