Is SPTA1 p.Arg115= (c.345G>A) pathogenic?

SPTA1 p.Arg115= (c.345G>A) is classified Conflicting classifications of pathogenicity in SPTA1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-08-30). Ultra-rare (popmax 0.066%, mid); Associated with pyropoikilocytosis, hereditary.

What condition is associated with SPTA1 p.Arg115= (c.345G>A)?

SPTA1 p.Arg115= (c.345G>A) is associated with pyropoikilocytosis, hereditary, elliptocytosis 2, hereditary spherocytosis type 3 (ClinVar).

How common is SPTA1 p.Arg115= (c.345G>A) in the general population?

SPTA1 p.Arg115= (c.345G>A) is ultra-rare (popmax 0.066%, mid) (gnomAD).

SPTA1 p.Arg115=

c.345G>A · rs200343758 · VCV293055

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.066%, mid)

Conditions

pyropoikilocytosis, hereditary

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 -1.1	GERP -4
Overall
CADD	2.294	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.066% Middle Eastern · 4/6,058 alleles

Filtering AF 0.0265% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0231%

Overall 0.0159% 257/1,613,330 alleles · ultra-rare exomes 226/1,461,186 · genomes 31/152,144 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.066%	1,514
South Asian	0.0362%	2,760
Remaining individualsnot grpmax-eligible	0.0288%	3,470
European (non-Finnish)	0.0167%	5,987
Admixed American	0.00501%	19,978
African / African-American	0.00267%	37,482

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.Arg115=
Coding: c.345G>A
MANE Select: NM_003126
dbSNP: rs200343758
Type: single nucleotide variant
Location: chr1:158683416 (GRCh38)
Gene constraint: LOEUF 0.591 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.74 · 3 PDB
Residue 115: an α-helix

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

Disease context

pyropoikilocytosis, hereditary — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: elliptocytosis 2 hereditary spherocytosis type 3

Similar variants

SPTA1 p.Arg115Trp Uncertain significance ★ ⚠ same residue
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

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-arg115 (accessed [today's date]).

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