Is SPTA1 p.Phe2417Ser (c.7250T>C) pathogenic?

SPTA1 p.Phe2417Ser (c.7250T>C) is classified Uncertain significance in SPTA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-09). AlphaMissense: likely pathogenic (0.7199); Very rare (popmax 0.000254%, nfe).

How common is SPTA1 p.Phe2417Ser (c.7250T>C) in the general population?

SPTA1 p.Phe2417Ser (c.7250T>C) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about SPTA1 p.Phe2417Ser (c.7250T>C)?

AlphaMissense predicts likely pathogenic (score 0.7199) — an in-silico prediction, not a clinical call.

SPTA1 p.Phe2417Ser

c.7250T>C · rs1229076536 · VCV2436367

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7199 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.7199	likely pathogenic
REVEL	0.385	indeterminate
SaProt	LLR -6.87	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 11	GERP 1.6, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 75 kb · p 2.2e-07 · regional, not allelic
Overall
CADD	24.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,179,716 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,613,686 alleles · very rare exomes 3/1,461,398 · genomes 0/152,288 · joint denominator

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: SPTA1
Protein: p.Phe2417Ser
Coding: c.7250T>C
MANE Select: NM_003126
dbSNP: rs1229076536
Type: single nucleotide variant
Location: chr1:158611274 (GRCh38)

Full SPTA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/spta1-p-phe2417ser (accessed [today's date]).

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