Is CHRND p.Val328Phe (c.982G>T) pathogenic?

CHRND p.Val328Phe (c.982G>T) is classified Uncertain significance in CHRND (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-19). AlphaMissense: likely pathogenic (0.6437); Very rare (popmax 0.00333%, amr); Associated with lethal multiple pterygium syndrome.

What condition is associated with CHRND p.Val328Phe (c.982G>T)?

CHRND p.Val328Phe (c.982G>T) is associated with lethal multiple pterygium syndrome (ClinVar).

How common is CHRND p.Val328Phe (c.982G>T) in the general population?

CHRND p.Val328Phe (c.982G>T) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about CHRND p.Val328Phe (c.982G>T)?

AlphaMissense predicts likely pathogenic (score 0.6437) — an in-silico prediction, not a clinical call.

CHRND p.Val328Phe

c.982G>T · rs762813704 · VCV2905748

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6437 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

lethal multiple pterygium syndrome

Computational evidence

Protein change
AlphaMissense	0.6437	likely pathogenic
REVEL	0.823	moderately pathogenic-leaning
SaProt	LLR -13.53	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 9,093 bp · p 0.12 · regional, not allelic
Overall
CADD	25.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/60,010 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000124% 2/1,613,932 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.Val328Phe
Coding: c.982G>T
MANE Select: NM_000751
dbSNP: rs762813704
Type: single nucleotide variant
Location: chr2:232531591 (GRCh38)
Gene constraint: LOEUF 0.848 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.21 · 25 PDB
Residue 328: 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.Val328Asp Uncertain significance ★ ⚠ same residue
CHRND p.Val328= Likely benign ★ same residue
CHRND p.Val328fs Pathogenic/Likely pathogenic ★★ same residue
CHRND p.Val328Ile 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

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-val328phe (accessed [today's date]).

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