Is CASQ1 p.Phe255= (c.765C>T) pathogenic?

CASQ1 p.Phe255= (c.765C>T) is classified Likely benign in CASQ1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-15). Ultra-rare (popmax 0.0417%, amr); Associated with Inborn genetic diseases.

What condition is associated with CASQ1 p.Phe255= (c.765C>T)?

CASQ1 p.Phe255= (c.765C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CASQ1 p.Phe255= (c.765C>T) in the general population?

CASQ1 p.Phe255= (c.765C>T) is ultra-rare (popmax 0.0417%, amr) (gnomAD).

CASQ1 p.Phe255=

c.765C>T · rs747477156 · VCV1652197

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0417%, amr)

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 -7.9	GERP -5.2
Overall
CADD	3.553	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0417% Admixed American · 25/59,982 alleles

Filtering AF 0.0289% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0248%

Overall 0.00242% 39/1,613,782 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0417%	2,399
Remaining individualsnot grpmax-eligible	0.0016%	62,470
South Asian	0.0011%	91,058
European (non-Finnish)	0.00102%	98,327

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.Phe255=
Coding: c.765C>T
MANE Select: NM_001231
dbSNP: rs747477156
Type: single nucleotide variant
Location: chr1:160196010 (GRCh38)
Gene constraint: LOEUF 0.965 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.51 · 6 PDB
Residue 255: an α-helix

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.Phe255Leu 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-phe255 (accessed [today's date]).

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