Is CHRND p.Pro271= (c.813G>A) pathogenic?

CHRND p.Pro271= (c.813G>A) is classified Likely benign in CHRND (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-18). Rare (popmax 0.111%, afr); Associated with lethal multiple pterygium syndrome.

What condition is associated with CHRND p.Pro271= (c.813G>A)?

CHRND p.Pro271= (c.813G>A) is associated with lethal multiple pterygium syndrome (ClinVar).

How common is CHRND p.Pro271= (c.813G>A) in the general population?

CHRND p.Pro271= (c.813G>A) is rare (popmax 0.111%, afr) (gnomAD).

CHRND p.Pro271=

c.813G>A · rs147073853 · VCV731176

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.111%, 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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -14	GERP -4.3
Overall
CADD	4.604	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.111% African / African-American · 83/74,960 alleles

Filtering AF 0.0915% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0844%

Overall 0.00607% 98/1,613,946 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.111%	903
Remaining individualsnot grpmax-eligible	0.0064%	15,626
East Asian	0.00446%	22,440
Admixed American	0.00167%	60,018
European (non-Finnish)	0.000678%	147,499

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.Pro271=
Coding: c.813G>A
MANE Select: NM_000751
dbSNP: rs147073853
Type: single nucleotide variant
Location: chr2:232530132 (GRCh38)
Gene constraint: LOEUF 0.848 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.21 · 25 PDB
Residue 271: a UniProt-annotated variant site (in cms3b; burst duration was decreased and disassociation of ach was increased resulting in brief channel opening episodes; shows abnormal association with alpha chrna1 subunit resulting in a decreased number of fully assembled achrs)

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.Pro271Gln Likely pathogenic ★ same residue
CHRND p.Pro271Leu 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-pro271 (accessed [today's date]).

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