Is CASC3 p.Asp24His (c.70G>C) pathogenic?

CASC3 p.Asp24His (c.70G>C) is classified Uncertain significance in CASC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-04). AlphaMissense: ambiguous (0.5251); Absent from gnomAD v4.1.

How common is CASC3 p.Asp24His (c.70G>C) in the general population?

CASC3 p.Asp24His (c.70G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CASC3 p.Asp24His (c.70G>C)?

AlphaMissense predicts ambiguous (score 0.5251) — an in-silico prediction, not a clinical call.

CASC3 p.Asp24His

c.70G>C · rs1988680976 · VCV2616347

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5251 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5251	ambiguous
REVEL	0.106	moderately benign-leaning
SaProt	LLR -9.26	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.4	GERP 0.64, phastCons 1
Regional constraint	o/e 1.30	unconstrained · MANE · 675 bp · p 0.00086 · regional, not allelic
Overall
CADD	29.7	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

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: CASC3
Protein: p.Asp24His
Coding: c.70G>C
MANE Select: NM_007359
dbSNP: rs1988680976
Type: single nucleotide variant
Location: chr17:40140618 (GRCh38)
Gene constraint: LOEUF 0.466 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 54.18 · 13 PDB
Residue 24: the 'disordered' region

Full CASC3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CASC3 p.Ala247Val Uncertain significance ★ ⚠ same type
CASC3 p.Ala380Gly Uncertain significance ★ ⚠ same type
CASC3 p.Ala472Val Uncertain significance ★ ⚠ same type
CASC3 p.Ala618Val Uncertain significance ★ ⚠ same type
CASC3 p.Ala641Thr Uncertain significance ★ ⚠ same type
CASC3 p.Ala670Thr Uncertain significance ★ ⚠ same type
CASC3 p.Ala72Ser Uncertain significance ★ ⚠ same type
CASC3 p.Arg207His 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/casc3-p-asp24his (accessed [today's date]).

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