Is CASQ1 p.Ala172= (c.516G>A) pathogenic?

CASQ1 p.Ala172= (c.516G>A) is classified Benign/Likely benign in CASQ1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-04). Rare (popmax 0.134%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CASQ1 p.Ala172= (c.516G>A)?

CASQ1 p.Ala172= (c.516G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CASQ1 p.Ala172= (c.516G>A) in the general population?

CASQ1 p.Ala172= (c.516G>A) is rare (popmax 0.134%, nfe) (gnomAD).

CASQ1 p.Ala172=

c.516G>A · rs55804336 · VCV725061

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.134%, nfe)

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 -3.8	GERP -5.2
Overall
CADD	6.091	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.134% European (non-Finnish) · 1,586/1,179,602 alleles

Filtering AF 0.129% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.127%

Overall 0.103% 1,665/1,613,358 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.134%	744
Remaining individualsnot grpmax-eligible	0.0624%	1,602
African / African-American	0.028%	3,571
Admixed American	0.0167%	5,993
Finnishnot grpmax-eligible	0.00625%	16,000
South Asian	0.00549%	18,207

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.Ala172=
Coding: c.516G>A
MANE Select: NM_001231
dbSNP: rs55804336
Type: single nucleotide variant
Location: chr1:160195062 (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

Disease context

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

Similar variants

CASQ1 p.Ala172Glu Uncertain significance ★ ⚠ same residue
CASQ1 p.Ala172Pro Uncertain significance ★★ ⚠ same residue
CASQ1 p.Ala172Val 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

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-ala172 (accessed [today's date]).

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