Is CASP14 p.Ter243= (c.729G>A) pathogenic?

CASP14 p.Ter243= (c.729G>A) is classified Likely benign in CASP14 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-18). Ultra-rare (popmax 0.0549%, amr).

How common is CASP14 p.Ter243= (c.729G>A) in the general population?

CASP14 p.Ter243= (c.729G>A) is ultra-rare (popmax 0.0549%, amr) (gnomAD).

CASP14 p.Ter243=

c.729G>A · rs202004752 · VCV1343637

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

stop-loss

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0549%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	stop-loss	predicted loss-of-function
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	GERP 0.037, phastCons 0.99
Overall
CADD	9.345	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0549% Admixed American · 31/56,510 alleles

Filtering AF 0.0397% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0345%

Overall 0.0141% 224/1,585,374 alleles · ultra-rare exomes 190/1,433,072 · genomes 34/152,302 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0549%	1,823
European (non-Finnish)	0.0158%	6,324
Remaining individualsnot grpmax-eligible	0.013%	7,685
African / African-American	0.00134%	74,546

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: CASP14
Protein: p.Ter243=
Coding: c.729G>A
MANE Select: NM_012114
dbSNP: rs202004752
Type: single nucleotide variant
Location: chr19:15056089 (GRCh38)
Gene constraint: LOEUF 1.217 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.44

Full CASP14 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CASP14 p.Met150Lys Uncertain significance ★★ ⚠ same type
CASP14 p.Tyr240Phe Uncertain significance ★★ ⚠ same type
CASP14 c.404-151A>C Benign ★★ same type
CASP14 c.404-271T>C Benign ★★ same type
CASP14 c.520+77T>C Benign ★★ same type
CASP14 c.625-34G>T Benign ★★ same type
CASP14 c.-46-101T>A Benign ★★ same type
CASP14 c.-46-259A>G Benign ★★ 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/casp14-p-ter243 (accessed [today's date]).

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