Is SNTA1 p.Pro174= (c.522G>A) pathogenic?

SNTA1 p.Pro174= (c.522G>A) is classified Likely benign in SNTA1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-01). Ultra-rare (popmax 0.0495%, mid); Associated with Cardiovascular phenotype.

What condition is associated with SNTA1 p.Pro174= (c.522G>A)?

SNTA1 p.Pro174= (c.522G>A) is associated with Cardiovascular phenotype, long QT syndrome (ClinVar).

How common is SNTA1 p.Pro174= (c.522G>A) in the general population?

SNTA1 p.Pro174= (c.522G>A) is ultra-rare (popmax 0.0495%, mid) (gnomAD).

SNTA1 p.Pro174=

c.522G>A · rs780808390 · VCV1149401

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0495%, mid)

Conditions

Cardiovascular phenotype

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 -5.8	GERP -3.7
Overall
CADD	4.665	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0495% Middle Eastern · 3/6,062 alleles

Filtering AF 0.0369% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.033%

Overall 0.00452% 73/1,613,668 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0495%	2,021
South Asian	0.0483%	2,070
Finnishnot grpmax-eligible	0.0281%	3,557
Remaining individualsnot grpmax-eligible	0.0032%	31,246
East Asian	0.00223%	44,876
Admixed American	0.00167%	59,990
European (non-Finnish)	0.000339%	294,902

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.Pro174=
Coding: c.522G>A
MANE Select: NM_003098
dbSNP: rs780808390
Type: single nucleotide variant
Location: chr20:33417898 (GRCh38)
Gene constraint: LOEUF 0.981 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.00
Residue 174: the ph 1 domain

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

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: long QT syndrome

Similar variants

SNTA1 p.Pro174Leu 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
SNTA1 p.Ala122Thr Uncertain significance ★★ ⚠ same condition
SNTA1 p.Ala255Pro 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-pro174 (accessed [today's date]).

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