Is CHRND p.Pro338Arg (c.1013C>G) pathogenic?

CHRND p.Pro338Arg (c.1013C>G) is classified Uncertain significance in CHRND (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-29). AlphaMissense: likely pathogenic (0.7941); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CHRND p.Pro338Arg (c.1013C>G)?

CHRND p.Pro338Arg (c.1013C>G) is associated with Inborn genetic diseases (ClinVar).

How common is CHRND p.Pro338Arg (c.1013C>G) in the general population?

CHRND p.Pro338Arg (c.1013C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHRND p.Pro338Arg (c.1013C>G)?

AlphaMissense predicts likely pathogenic (score 0.7941) — an in-silico prediction, not a clinical call.

CHRND p.Pro338Arg

c.1013C>G · VCV4002681

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7941 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7941	likely pathogenic
REVEL	0.848	moderately pathogenic-leaning
SaProt	LLR -14.14	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 5.8	GERP 1.1, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 9,093 bp · p 0.12 · regional, not allelic
Overall
CADD	23.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CHRND
Protein: p.Pro338Arg
Coding: c.1013C>G
MANE Select: NM_000751
Type: single nucleotide variant
Location: chr2:232531622 (GRCh38)
Gene constraint: LOEUF 0.848 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.21 · 25 PDB
Residue 338: a turn

Full CHRND gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CHRND p.Arg102Cys Uncertain significance ★★ ⚠ same condition
CHRND p.Arg102His Uncertain significance ★★ ⚠ same condition
CHRND p.Arg148His Uncertain significance ★★ ⚠ same condition
CHRND p.Arg191His Uncertain significance ★★ ⚠ same condition
CHRND p.Arg298Cys Uncertain significance ★★ ⚠ same condition
CHRND p.Arg30Gln Uncertain significance ★★ ⚠ same condition
CHRND p.Arg30Trp Uncertain significance ★★ ⚠ same condition
CHRND p.Arg412Lys Uncertain significance ★★ ⚠ 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-pro338arg (accessed [today's date]).

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