Is CASP5 p.Val39Met (c.115G>A) pathogenic?

CASP5 p.Val39Met (c.115G>A) is classified Likely benign in CASP5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-04). AlphaMissense: likely benign (0.0923); Ultra-rare (popmax 0.048%, afr).

How common is CASP5 p.Val39Met (c.115G>A) in the general population?

CASP5 p.Val39Met (c.115G>A) is ultra-rare (popmax 0.048%, afr) (gnomAD).

What do computational predictors say about CASP5 p.Val39Met (c.115G>A)?

AlphaMissense predicts likely benign (score 0.0923) — an in-silico prediction, not a clinical call.

CASP5 p.Val39Met

c.115G>A · rs144740986 · VCV3137606

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0923 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.048%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0923	likely benign
REVEL	0.005	strongly benign-leaning
SaProt	LLR -8.24	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.1
Regional constraint	o/e 0.96	unconstrained · MANE · 27 kb · p 0.38 · regional, not allelic
Overall
CADD	1.928	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 0.048% African / African-American · 36/75,000 alleles

Filtering AF 0.0356% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0313%

Overall 0.00973% 157/1,613,080 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.048%	2,083
Admixed American	0.02%	4,988
European (non-Finnish)	0.00873%	11,450
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,570
Remaining individualsnot grpmax-eligible	0.0032%	31,236
East Asian	0.00223%	44,850
Finnishnot grpmax-eligible	0.00156%	63,982
South Asian	0.0011%	91,058

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: CASP5
Protein: p.Val39Met
Coding: c.115G>A
MANE Select: NM_004347
dbSNP: rs144740986
Type: single nucleotide variant
Location: chr11:105008873 (GRCh38)
Gene constraint: LOEUF 1.044 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.62

Full CASP5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CASP5 p.Ala195Thr Uncertain significance ★ ⚠ same type
CASP5 p.Ala359Val Uncertain significance ★ ⚠ same type
CASP5 p.Arg11Cys Uncertain significance ★ ⚠ same type
CASP5 p.Arg120Gln Uncertain significance ★ ⚠ same type
CASP5 p.Arg123Cys Uncertain significance ★ ⚠ same type
CASP5 p.Arg168Cys Uncertain significance ★ ⚠ same type
CASP5 p.Arg191Cys Uncertain significance ★ ⚠ same type
CASP5 p.Arg191His 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/casp5-p-val39met (accessed [today's date]).

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