Is CASP5 p.Phe261Ser (c.782T>C) pathogenic?

CASP5 p.Phe261Ser (c.782T>C) is classified Uncertain significance in CASP5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-29). AlphaMissense: likely pathogenic (0.957); Absent from gnomAD v4.1.

How common is CASP5 p.Phe261Ser (c.782T>C) in the general population?

CASP5 p.Phe261Ser (c.782T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CASP5 p.Phe261Ser (c.782T>C)?

AlphaMissense predicts likely pathogenic (score 0.957) — an in-silico prediction, not a clinical call.

CASP5 p.Phe261Ser

c.782T>C · VCV3995629

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.957 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.957	likely pathogenic · top 1% in CASP5
REVEL	0.473	indeterminate
SaProt	LLR -16.32	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.9	phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 27 kb · p 0.38 · regional, not allelic
Overall
CADD	24.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CASP5
Protein: p.Phe261Ser
Coding: c.782T>C
MANE Select: NM_004347
Type: single nucleotide variant
Location: chr11:105000431 (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-phe261ser (accessed [today's date]).

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