Is CASQ1 p.Pro9= (c.27C>A) pathogenic?

CASQ1 p.Pro9= (c.27C>A) is classified Benign/Likely benign in CASQ1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-01). Low-frequency (popmax 2.53%, afr); Associated with Inborn genetic diseases.

What condition is associated with CASQ1 p.Pro9= (c.27C>A)?

CASQ1 p.Pro9= (c.27C>A) is associated with Inborn genetic diseases (ClinVar).

How common is CASQ1 p.Pro9= (c.27C>A) in the general population?

CASQ1 p.Pro9= (c.27C>A) is low-frequency (popmax 2.53%, afr) (gnomAD).

CASQ1 p.Pro9=

c.27C>A · rs76394704 · VCV716832

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.53%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7	GERP 1.9, phastCons 1
Overall
CADD	10.98	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.53% African / African-American · 1,899/75,006 alleles

Filtering AF 2.44% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.4%

Overall 0.156% 2,517/1,614,068 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.53%	39
Middle Eastern	0.528%	189
Ashkenazi Jewishnot grpmax-eligible	0.443%	226
Remaining individualsnot grpmax-eligible	0.216%	463
Admixed American	0.208%	480
European (non-Finnish)	0.0153%	6,519
South Asian	0.0143%	7,006
Finnishnot grpmax-eligible	0.00156%	64,026

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: CASQ1
Protein: p.Pro9=
Coding: c.27C>A
MANE Select: NM_001231
dbSNP: rs76394704
Type: single nucleotide variant
Location: chr1:160190778 (GRCh38)
Gene constraint: LOEUF 0.965 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.51 · 6 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CASQ1 p.Pro9His Uncertain significance ★ ⚠ same residue
CASQ1 p.Ala115Val Uncertain significance ★★ ⚠ same condition
CASQ1 p.Ala289Val Uncertain significance ★★ ⚠ same condition
CASQ1 p.Arg16Gln Uncertain significance ★★ ⚠ same condition
CASQ1 p.Arg16Trp Uncertain significance ★★ ⚠ same condition
CASQ1 p.Asp159Gly Uncertain significance ★★ ⚠ same condition
CASQ1 p.Asp309Asn Uncertain significance ★★ ⚠ same condition
CASQ1 p.Asp363Asn Uncertain significance ★★ ⚠ same condition

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-pro9 (accessed [today's date]).

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