Is CHRND p.Pro356= (c.1068G>A) pathogenic?

CHRND p.Pro356= (c.1068G>A) is classified Likely benign in CHRND (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-07). Very rare (popmax 0.00879%, sas); Associated with lethal multiple pterygium syndrome.

What condition is associated with CHRND p.Pro356= (c.1068G>A)?

CHRND p.Pro356= (c.1068G>A) is associated with lethal multiple pterygium syndrome (ClinVar).

How common is CHRND p.Pro356= (c.1068G>A) in the general population?

CHRND p.Pro356= (c.1068G>A) is very rare (popmax 0.00879%, sas) (gnomAD).

CHRND p.Pro356=

c.1068G>A · rs748794171 · VCV2739819

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00879%, sas)

Conditions

lethal multiple pterygium syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.59 · evaluated, not missing
Constraint at this position
Conservation	phyloP -12	GERP -3.7
Overall
CADD	0.556	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00879% South Asian · 8/91,052 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00312%

Overall 0.00273% 44/1,612,846 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00879%	11,381
Remaining individualsnot grpmax-eligible	0.00321%	31,196
European (non-Finnish)	0.00263%	38,062
East Asian	0.00223%	44,892
Admixed American	0.00167%	59,988
African / African-American	0.00134%	74,898

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.Pro356=
Coding: c.1068G>A
MANE Select: NM_000751
dbSNP: rs748794171
Type: single nucleotide variant
Location: chr2:232533951 (GRCh38)
Gene constraint: LOEUF 0.848 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.21 · 25 PDB
Residue 356: 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

Similar variants

CHRND p.Pro356Leu Uncertain significance ★★ ⚠ same residue
CHRND p.Pro356Ser Uncertain significance ★★ ⚠ same residue
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

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-pro356 (accessed [today's date]).

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