Is CHRND p.Arg102His (c.305G>A) pathogenic?

CHRND p.Arg102His (c.305G>A) is classified Uncertain significance in CHRND (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-03-27). AlphaMissense: ambiguous (0.4781); Ultra-rare (popmax 0.0147%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CHRND p.Arg102His (c.305G>A)?

CHRND p.Arg102His (c.305G>A) is associated with Inborn genetic diseases, lethal multiple pterygium syndrome (ClinVar).

How common is CHRND p.Arg102His (c.305G>A) in the general population?

CHRND p.Arg102His (c.305G>A) is ultra-rare (popmax 0.0147%, nfe) (gnomAD).

What do computational predictors say about CHRND p.Arg102His (c.305G>A)?

AlphaMissense predicts ambiguous (score 0.4781) — an in-silico prediction, not a clinical call.

CHRND p.Arg102His

c.305G>A · rs147919651 · VCV466192

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.4781 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0147%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4781	ambiguous
REVEL	0.76	pathogenic-leaning
SaProt	LLR -6.91	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 9,093 bp · p 0.12 · regional, not allelic
Overall
CADD	27.1	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0147% European (non-Finnish) · 174/1,180,016 alleles

Filtering AF 0.0129% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0123%

Overall 0.0123% 198/1,614,078 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0147%	6,782
Admixed American	0.0133%	7,501
Remaining individualsnot grpmax-eligible	0.0128%	7,813
East Asian	0.00892%	11,217
African / African-American	0.00533%	18,749

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.Arg102His
Coding: c.305G>A
MANE Select: NM_000751
dbSNP: rs147919651
Type: single nucleotide variant
Location: chr2:232528323 (GRCh38)
Gene constraint: LOEUF 0.848 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.21 · 25 PDB
Residue 102: a β-strand

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

Also linked: lethal multiple pterygium syndrome

Similar variants

CHRND p.Arg102Cys Uncertain significance ★★ ⚠ same residue
CHRND p.Arg102Ser 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-arg102his (accessed [today's date]).

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