Is SNTA1 p.Ser259= (c.777G>A) pathogenic?

SNTA1 p.Ser259= (c.777G>A) is classified Likely benign in SNTA1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-28). Very rare (popmax 0.00167%, amr); Associated with Cardiovascular phenotype.

What condition is associated with SNTA1 p.Ser259= (c.777G>A)?

SNTA1 p.Ser259= (c.777G>A) is associated with Cardiovascular phenotype, long QT syndrome (ClinVar).

How common is SNTA1 p.Ser259= (c.777G>A) in the general population?

SNTA1 p.Ser259= (c.777G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

SNTA1 p.Ser259=

c.777G>A · rs1202456575 · VCV1760591

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

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 -10	GERP -3.7
Overall
CADD	0.309	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,006 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000342% 5/1,461,358 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,006
European (non-Finnish)	0.000339%	294,991

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.Ser259=
Coding: c.777G>A
MANE Select: NM_003098
dbSNP: rs1202456575
Type: single nucleotide variant
Location: chr20:33412707 (GRCh38)
Gene constraint: LOEUF 0.981 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.00
Residue 259: 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.Ser259Leu Uncertain significance ★★ ⚠ same residue
SNTA1 p.Ser259Ala Uncertain significance ★ ⚠ same residue
SNTA1 p.Ser259Ter 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-ser259 (accessed [today's date]).

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