Is CASP12 p.Arg203Cys (c.607C>T) pathogenic?

CASP12 p.Arg203Cys (c.607C>T) is classified Uncertain significance in CASP12 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-27). Ultra-rare (popmax 0.0167%, mid).

How common is CASP12 p.Arg203Cys (c.607C>T) in the general population?

CASP12 p.Arg203Cys (c.607C>T) is ultra-rare (popmax 0.0167%, mid) (gnomAD).

CASP12 p.Arg203Cys

c.607C>T · rs185140650 · VCV3137575

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.028	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.2	GERP -3.9
Overall
CADD	9.448	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0167% Middle Eastern · 1/5,982 alleles

Filtering AF 0.00178% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00138%

Overall 0.00228% 35/1,536,896 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0167%	5,982
African / African-American	0.00548%	18,263
East Asian	0.00489%	20,469
European (non-Finnish)	0.00235%	42,470
Remaining individualsnot grpmax-eligible	0.00166%	60,084

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: CASP12
Protein: p.Arg203Cys
Coding: c.607C>T
dbSNP: rs185140650
Type: single nucleotide variant
Location: chr11:104891230 (GRCh38)
Structure: AlphaFold pLDDT 77.13
Residue 203: a UniProt-annotated variant site (in)

Full CASP12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CASP12 p.Arg203His Uncertain significance ★ same residue
CASP12 p.Arg125Ter Likely benign ★★ same type
CASP12 c.1013T>G Uncertain significance ★ same type
CASP12 c.107T>C Uncertain significance ★ same type
CASP12 c.19T>A Uncertain significance ★ same type
CASP12 c.22A>G Uncertain significance ★ same type
CASP12 c.254G>A Uncertain significance ★ same type
CASP12 c.269G>C 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/casp12-p-arg203cys (accessed [today's date]).

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