Is SNTA1 p.Pro75= (c.225G>A) pathogenic?

SNTA1 p.Pro75= (c.225G>A) is classified Likely benign in SNTA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-02-14). Very rare (popmax 9.39e-05%, nfe); Associated with long QT syndrome.

What condition is associated with SNTA1 p.Pro75= (c.225G>A)?

SNTA1 p.Pro75= (c.225G>A) is associated with long QT syndrome (ClinVar).

How common is SNTA1 p.Pro75= (c.225G>A) in the general population?

SNTA1 p.Pro75= (c.225G>A) is very rare (popmax 9.39e-05%, nfe) (gnomAD).

SNTA1 p.Pro75=

c.225G>A · rs2146814729 · VCV1152419

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 9.39e-05%, nfe)

Conditions

long QT syndrome

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 -0.01	GERP -1.9, phastCons 0.85
Overall
CADD	11.29	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 9.39e-05% European (non-Finnish) · 1/1,065,370 alleles

Overall 8.25e-05% 1/1,212,196 alleles · very rare

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: SNTA1
Protein: p.Pro75=
Coding: c.225G>A
MANE Select: NM_003098
dbSNP: rs2146814729
Type: single nucleotide variant
Location: chr20:33443396 (GRCh38)
Gene constraint: LOEUF 0.981 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.00
Residue 75: the ph 1 domain; the 'disordered' region

Full SNTA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

long QT syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SNTA1 p.Pro75Arg Uncertain significance ★ ⚠ same residue
SNTA1 p.Pro75Leu Uncertain significance ★ ⚠ same residue
SNTA1 p.Pro75Ser Uncertain significance ★ ⚠ same residue
SNTA1 c.1425+1G>A Uncertain significance ★★ same condition
SNTA1 c.497-3C>T Uncertain significance ★★ same condition
SNTA1 c.497-5A>G Uncertain significance ★★ same condition
SNTA1 c.702-3C>T Uncertain significance ★★ same condition
SNTA1 c.910-3C>T 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/snta1-p-pro75 (accessed [today's date]).

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