Is CASP10 p.Arg21Pro (c.62G>C) pathogenic?

CASP10 p.Arg21Pro (c.62G>C) is classified Uncertain significance in CASP10 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-26). AlphaMissense: likely pathogenic (0.6428); Very rare (popmax 0.00668%, eas).

How common is CASP10 p.Arg21Pro (c.62G>C) in the general population?

CASP10 p.Arg21Pro (c.62G>C) is very rare (popmax 0.00668%, eas) (gnomAD).

What do computational predictors say about CASP10 p.Arg21Pro (c.62G>C)?

AlphaMissense predicts likely pathogenic (score 0.6428) — an in-silico prediction, not a clinical call.

CASP10 p.Arg21Pro

c.62G>C · VCV3995584

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6428 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6428	likely pathogenic
REVEL	0.591	indeterminate
SaProt	LLR -8.32	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.92	GERP 1.7
Regional constraint	o/e 1.00	unconstrained · MANE · 32 kb · p 0.98 · regional, not allelic
Overall
CADD	20.5	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 0.00668% East Asian · 3/44,882 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000342% 5/1,461,858 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00668%	14,961
European (non-Finnish)	0.000169%	589,998

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: CASP10
Protein: p.Arg21Pro
Coding: c.62G>C
MANE Select: NM_032977
Type: single nucleotide variant
Location: chr2:201185839 (GRCh38)
Gene constraint: LOEUF 1.046 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 69.54
Residue 21: a UniProt-annotated variant site (found in a multiple myeloma sample; somatic mutation); the ded 1 domain

Full CASP10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CASP10 p.Arg21His Uncertain significance ★★ ⚠ same residue
CASP10 p.Arg21Cys Uncertain significance ★ ⚠ same residue
CASP10 c.1415+2T>C Uncertain significance ★★ same type
CASP10 c.1416-3C>A Uncertain significance ★★ same type
CASP10 c.347+2T>G Uncertain significance ★★ same type
CASP10 c.684+1G>A Uncertain significance ★★ same type
CASP10 c.922+5G>A Uncertain significance ★★ same type
CASP10 p.Ala237Glu Uncertain significance ★★ ⚠ same type

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/casp10-p-arg21pro (accessed [today's date]).

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