Is CASQ1 p.Ala172Pro (c.514G>C) pathogenic?

CASQ1 p.Ala172Pro (c.514G>C) is classified Uncertain significance in CASQ1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-12-01). AlphaMissense: likely pathogenic (0.964); Absent from gnomAD v4.1.

How common is CASQ1 p.Ala172Pro (c.514G>C) in the general population?

CASQ1 p.Ala172Pro (c.514G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CASQ1 p.Ala172Pro (c.514G>C)?

AlphaMissense predicts likely pathogenic (score 0.964) — an in-silico prediction, not a clinical call.

CASQ1 p.Ala172Pro

c.514G>C · rs2525055291 · VCV2107739

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.964 · 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	0.964	likely pathogenic
REVEL	0.626	indeterminate
SaProt	LLR -12.79	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 2.6, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 11 kb · p 0.42 · regional, not allelic
Overall
CADD	29.0	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

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: CASQ1
Protein: p.Ala172Pro
Coding: c.514G>C
MANE Select: NM_001231
dbSNP: rs2525055291
Type: single nucleotide variant
Location: chr1:160195060 (GRCh38)
Gene constraint: LOEUF 0.965 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.51 · 6 PDB
Residue 172: an α-helix

Full CASQ1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CASQ1 p.Ala172Val Uncertain significance ★★ ⚠ same residue
CASQ1 p.Ala172= Benign/Likely benign ★★ same residue
CASQ1 p.Ala172Glu Uncertain significance ★ ⚠ same residue
CASQ1 p.Ala172fs Uncertain significance ★ same residue
CASQ1 p.Asp244Gly Pathogenic ★★ ⚠ same type
CASQ1 c.279+1G>A Uncertain significance ★★ same type
CASQ1 c.984+2T>G Uncertain significance ★★ same type
CASQ1 c.985-1G>A 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/casq1-p-ala172pro (accessed [today's date]).

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