Is SLC8A1 p.Ile571= (c.1713C>T) pathogenic?

SLC8A1 p.Ile571= (c.1713C>T) is classified Likely benign in SLC8A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-06-20). Very rare (popmax 0.00659%, sas).

How common is SLC8A1 p.Ile571= (c.1713C>T) in the general population?

SLC8A1 p.Ile571= (c.1713C>T) is very rare (popmax 0.00659%, sas) (gnomAD).

SLC8A1 p.Ile571=

c.1713C>T · rs774752331 · VCV750473

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00659%, sas)

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 -1.8	GERP -2.1
Overall
CADD	7.044	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00659% South Asian · 6/91,076 alleles

Filtering AF 0.00286% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00195%

Overall 0.00149% 24/1,613,614 alleles · very rare exomes 22/1,461,662 · genomes 2/151,952 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00659%	15,179
Remaining individualsnot grpmax-eligible	0.0064%	15,618
East Asian	0.00223%	44,862
African / African-American	0.00134%	74,856
European (non-Finnish)	0.00102%	98,326

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.Ile571=
Coding: c.1713C>T
MANE Select: NM_021097
dbSNP: rs774752331
Type: single nucleotide variant
Location: chr2:40428568 (GRCh38)
Gene constraint: LOEUF 0.363 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.64 · 5 PDB
Residue 571: a β-strand; the calx-beta 2 domain

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-ile571 (accessed [today's date]).

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