Is CASP7 p.Ala270Val (c.809C>T) pathogenic?

CASP7 p.Ala270Val (c.809C>T) is classified Uncertain significance in CASP7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-30). AlphaMissense: likely pathogenic (0.9215); Absent from gnomAD v4.1.

How common is CASP7 p.Ala270Val (c.809C>T) in the general population?

CASP7 p.Ala270Val (c.809C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CASP7 p.Ala270Val (c.809C>T)?

AlphaMissense predicts likely pathogenic (score 0.9215) — an in-silico prediction, not a clinical call.

CASP7 p.Ala270Val

c.809C>T · VCV3485222

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9215 · 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	0.9215	likely pathogenic
REVEL	0.621	indeterminate
SaProt	LLR -11.96	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 7.7	GERP 2.5, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 32 kb · p 0.049 · regional, not allelic
Overall
CADD	26.3	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: CASP7
Protein: p.Ala270Val
Coding: c.809C>T
MANE Select: NM_001227
Type: single nucleotide variant
Location: chr10:113729437 (GRCh38)
Gene constraint: LOEUF 0.993 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.05 · 47 PDB
Residue 270: an α-helix

Full CASP7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CASP7 p.Ala270Ser Uncertain significance ★ ⚠ same residue
CASP7 p.Asp255Glu Benign ★★ same type
CASP7 p.Ala164Val Uncertain significance ★ ⚠ same type
CASP7 p.Arg210Gln Uncertain significance ★ ⚠ same type
CASP7 p.Arg28Gln Uncertain significance ★ ⚠ same type
CASP7 p.Arg52Gln Uncertain significance ★ ⚠ same type
CASP7 p.Asn61Lys Uncertain significance ★ ⚠ same type
CASP7 p.Asp121Glu 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/casp7-p-ala270val (accessed [today's date]).

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