Is CHRND p.Tyr136= (c.408C>T) pathogenic?

CHRND p.Tyr136= (c.408C>T) is classified Likely benign in CHRND (ClinVar, Single submitter, 3 submitters; last evaluated 2025-11-05). Rare (popmax 0.177%, afr); Associated with lethal multiple pterygium syndrome.

What condition is associated with CHRND p.Tyr136= (c.408C>T)?

CHRND p.Tyr136= (c.408C>T) is associated with lethal multiple pterygium syndrome (ClinVar).

How common is CHRND p.Tyr136= (c.408C>T) in the general population?

CHRND p.Tyr136= (c.408C>T) is rare (popmax 0.177%, afr) (gnomAD).

CHRND p.Tyr136=

c.408C>T · rs112921420 · VCV128759

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.177%, afr)

Conditions

lethal multiple pterygium syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.202	benign-leaning
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.41 · evaluated, not missing
Constraint at this position
Conservation	phyloP -16	GERP -4.3
Overall
CADD	0.004	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.177% African / African-American · 133/75,040 alleles

Filtering AF 0.153% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.143%

Overall 0.0123% 199/1,614,168 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.177%	564
South Asian	0.0165%	6,072
Remaining individualsnot grpmax-eligible	0.0144%	6,946
Admixed American	0.01%	10,004
European (non-Finnish)	0.00297%	33,715
East Asian	0.00223%	44,876

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.Tyr136=
Coding: c.408C>T
MANE Select: NM_000751
dbSNP: rs112921420
Type: single nucleotide variant
Location: chr2:232528555 (GRCh38)
Gene constraint: LOEUF 0.848 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.21 · 25 PDB

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

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-tyr136 (accessed [today's date]).

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