Is SLC8A1 p.Ser903Phe (c.2708C>T) pathogenic?

SLC8A1 p.Ser903Phe (c.2708C>T) is classified Uncertain significance in SLC8A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-27). AlphaMissense: ambiguous (0.401); Ultra-rare (popmax 0.0535%, eas).

How common is SLC8A1 p.Ser903Phe (c.2708C>T) in the general population?

SLC8A1 p.Ser903Phe (c.2708C>T) is ultra-rare (popmax 0.0535%, eas) (gnomAD).

What do computational predictors say about SLC8A1 p.Ser903Phe (c.2708C>T)?

AlphaMissense predicts ambiguous (score 0.401) — an in-silico prediction, not a clinical call.

SLC8A1 p.Ser903Phe

c.2708C>T · rs201804871 · VCV2349241

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.401 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0535%, eas)

Computational evidence

Protein change
AlphaMissense	0.401	ambiguous
REVEL	0.295	indeterminate
SaProt	LLR -8.92	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Overall
CADD	26.3	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 0.0535% East Asian · 24/44,876 alleles

Filtering AF 0.0368% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0313%

Overall 0.00161% 26/1,614,176 alleles · ultra-rare exomes 19/1,461,886 · genomes 7/152,290 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0535%	1,870
European (non-Finnish)	0.000169%	590,012

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.Ser903Phe
Coding: c.2708C>T
MANE Select: NM_021097
dbSNP: rs201804871
Type: single nucleotide variant
Location: chr2:40115467 (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-ser903phe (accessed [today's date]).

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