Is CASP7 p.Gly89Arg (c.265G>A) pathogenic?

CASP7 p.Gly89Arg (c.265G>A) is classified Uncertain significance in CASP7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-08). AlphaMissense: likely pathogenic (0.9916); Ultra-rare (popmax 0.0111%, eas).

How common is CASP7 p.Gly89Arg (c.265G>A) in the general population?

CASP7 p.Gly89Arg (c.265G>A) is ultra-rare (popmax 0.0111%, eas) (gnomAD).

What do computational predictors say about CASP7 p.Gly89Arg (c.265G>A)?

AlphaMissense predicts likely pathogenic (score 0.9916) — an in-silico prediction, not a clinical call.

CASP7 p.Gly89Arg

c.265G>A · VCV3995634

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9916 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9916	likely pathogenic · top 7% in CASP7
REVEL	0.601	indeterminate
SaProt	LLR -14.69	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 12	GERP 2.3, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 32 kb · p 0.049 · regional, not allelic
Overall
CADD	34.0	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

Grpmax group 0.0111% East Asian · 5/44,890 alleles

Filtering AF 0.00434% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.00124% 20/1,614,044 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0111%	8,978
Remaining individualsnot grpmax-eligible	0.0096%	10,415
Admixed American	0.00167%	60,008
South Asian	0.0011%	91,090
European (non-Finnish)	0.000593%	168,576

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: CASP7
Protein: p.Gly89Arg
Coding: c.265G>A
MANE Select: NM_001227
Type: single nucleotide variant
Location: chr10:113721668 (GRCh38)
Gene constraint: LOEUF 0.993 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.05 · 47 PDB

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

Similar variants

CASP7 p.Asp255Glu Benign ★★ same type
CASP7 p.Ala164Val Uncertain significance ★ ⚠ same type
CASP7 p.Ala270Ser Uncertain significance ★ ⚠ same type
CASP7 p.Ala270Val 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

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-gly89arg (accessed [today's date]).

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