Is SPTA1 p.Ala720= (c.2160C>T) pathogenic?

SPTA1 p.Ala720= (c.2160C>T) is classified Conflicting classifications of pathogenicity in SPTA1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2022-02-11). Rare (popmax 0.12%, eas); Associated with elliptocytosis 2.

What condition is associated with SPTA1 p.Ala720= (c.2160C>T)?

SPTA1 p.Ala720= (c.2160C>T) is associated with elliptocytosis 2, pyropoikilocytosis, hereditary, hereditary spherocytosis type 3 (ClinVar).

How common is SPTA1 p.Ala720= (c.2160C>T) in the general population?

SPTA1 p.Ala720= (c.2160C>T) is rare (popmax 0.12%, eas) (gnomAD).

How is Hereditary elliptocytosis inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

SPTA1 p.Ala720=

c.2160C>T · rs199815523 · VCV293021

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.12%, eas)

Conditions

elliptocytosis 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -4.9	GERP -3.8
Overall
CADD	1.269	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.12% East Asian · 54/44,840 alleles

Filtering AF 0.0947% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0855%

Overall 0.00706% 114/1,613,818 alleles · rare exomes 112/1,461,724 · genomes 2/152,094 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.12%	830
Remaining individualsnot grpmax-eligible	0.0224%	4,464
European (non-Finnish)	0.00373%	26,817
Admixed American	0.00167%	59,994
South Asian	0.0011%	91,068

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.Ala720=
Coding: c.2160C>T
MANE Select: NM_003126
dbSNP: rs199815523
Type: single nucleotide variant
Location: chr1:158666376 (GRCh38)
Gene constraint: LOEUF 0.591 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.74 · 3 PDB

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

Disease context

elliptocytosis 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: pyropoikilocytosis, hereditary hereditary spherocytosis type 3

For Hereditary elliptocytosis (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: All ages
Prevalence: 1-5 / 10 000 (Worldwide)

Similar variants

SPTA1 c.1833+1G>A Pathogenic/Likely pathogenic ★★ same condition
SPTA1 c.2806-13T>G Pathogenic/Likely pathogenic ★★ same condition
SPTA1 c.4339-99C>T Pathogenic/Likely pathogenic ★★ same condition
SPTA1 c.6788+11C>T Pathogenic ★★ same condition
SPTA1 p.Arg1047Ter Pathogenic ★★ same condition
SPTA1 p.Arg1659Ter Pathogenic ★★ same condition
SPTA1 p.Arg28Cys Pathogenic/Likely pathogenic ★★ same condition
SPTA1 p.Arg28His Pathogenic/Likely pathogenic ★★ 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/spta1-p-ala720 (accessed [today's date]).

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