Is SNTA1 p.Pro74= (c.222C>G) pathogenic?

SNTA1 p.Pro74= (c.222C>G) is classified Likely benign in SNTA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-12-04). Very rare (popmax 0.000188%, nfe); Associated with long QT syndrome.

What condition is associated with SNTA1 p.Pro74= (c.222C>G)?

SNTA1 p.Pro74= (c.222C>G) is associated with long QT syndrome (ClinVar).

How common is SNTA1 p.Pro74= (c.222C>G) in the general population?

SNTA1 p.Pro74= (c.222C>G) is very rare (popmax 0.000188%, nfe) (gnomAD).

SNTA1 p.Pro74=

c.222C>G · rs752864338 · VCV1593299

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000188%, 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 0.98	GERP -3, phastCons 1
Overall
CADD	8.398	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000188% European (non-Finnish) · 2/1,063,764 alleles

Filtering AF 3.1e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.2e-05%

Overall 0.000166% 2/1,208,432 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.Pro74=
Coding: c.222C>G
MANE Select: NM_003098
dbSNP: rs752864338
Type: single nucleotide variant
Location: chr20:33443399 (GRCh38)
Gene constraint: LOEUF 0.981 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.00
Residue 74: 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.Pro74Ser Uncertain significance ★★ ⚠ same residue
SNTA1 p.Pro74Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
SNTA1 p.Pro74Thr Uncertain significance ★ ⚠ same residue
SNTA1 p.Pro74Ala 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

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-pro74 (accessed [today's date]).

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