Is CASP5 p.Gln313Arg (c.938A>G) pathogenic?

CASP5 p.Gln313Arg (c.938A>G) is classified Uncertain significance in CASP5 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-10). AlphaMissense: likely pathogenic (0.7756); Very rare (popmax 0.00446%, eas).

How common is CASP5 p.Gln313Arg (c.938A>G) in the general population?

CASP5 p.Gln313Arg (c.938A>G) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about CASP5 p.Gln313Arg (c.938A>G)?

AlphaMissense predicts likely pathogenic (score 0.7756) — an in-silico prediction, not a clinical call.

CASP5 p.Gln313Arg

c.938A>G · rs754647597 · VCV2276773

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7756 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7756	likely pathogenic
REVEL	0.543	indeterminate
SaProt	LLR -11.62	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 4.7	phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 27 kb · p 0.38 · regional, not allelic
Overall
CADD	26.6	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 0.00446% East Asian · 2/44,888 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000137% 2/1,461,860 alleles · very rare

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.Gln313Arg
Coding: c.938A>G
MANE Select: NM_004347
dbSNP: rs754647597
Type: single nucleotide variant
Location: chr11:105000275 (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-gln313arg (accessed [today's date]).

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