Is SLC8A1 p.Tyr2Phe (c.5A>T) pathogenic?

SLC8A1 p.Tyr2Phe (c.5A>T) is classified Likely benign in SLC8A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-06-05). AlphaMissense: likely benign (0.0603); Rare (popmax 0.499%, afr).

How common is SLC8A1 p.Tyr2Phe (c.5A>T) in the general population?

SLC8A1 p.Tyr2Phe (c.5A>T) is rare (popmax 0.499%, afr) (gnomAD).

What do computational predictors say about SLC8A1 p.Tyr2Phe (c.5A>T)?

AlphaMissense predicts likely benign (score 0.0603) — an in-silico prediction, not a clinical call.

SLC8A1 p.Tyr2Phe

c.5A>T · rs115564742 · VCV747226

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0603 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.499%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0603	likely benign
REVEL	0.037	moderately benign-leaning
SaProt	LLR -5.28	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.7	GERP -5.8
Overall
CADD	2.286	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 0.499% African / African-American · 373/74,716 alleles

Filtering AF 0.457% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.441%

Overall 0.0255% 410/1,605,452 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.499%	200
Remaining individualsnot grpmax-eligible	0.0306%	3,270
Admixed American	0.0237%	4,223
European (non-Finnish)	0.00034%	293,990

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: SLC8A1
Protein: p.Tyr2Phe
Coding: c.5A>T
MANE Select: NM_021097
dbSNP: rs115564742
Type: single nucleotide variant
Location: chr2:40430276 (GRCh38)
Gene constraint: LOEUF 0.363 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.64 · 5 PDB

Full SLC8A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SLC8A1 p.Arg929= Benign ★★ same type
SLC8A1 p.Gly905= Benign ★★ same type
SLC8A1 p.Ala307Val Uncertain significance ★ ⚠ same type
SLC8A1 p.Ala322Val Uncertain significance ★ ⚠ same type
SLC8A1 p.Ala349Gly Uncertain significance ★ ⚠ same type
SLC8A1 p.Ala451Ser Uncertain significance ★ ⚠ same type
SLC8A1 p.Ala504Gly Uncertain significance ★ ⚠ same type
SLC8A1 p.Ala512Thr Uncertain significance ★ ⚠ same type

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/slc8a1-p-tyr2phe (accessed [today's date]).

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