Is SPTA1 p.Pro1986= (c.5958C>T) pathogenic?

SPTA1 p.Pro1986= (c.5958C>T) is classified Benign/Likely benign in SPTA1 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-03). Common (popmax 43.1%, afr) — too common for a highly-penetrant pathogenic allele; Associated with hereditary spherocytosis type 3.

What condition is associated with SPTA1 p.Pro1986= (c.5958C>T)?

SPTA1 p.Pro1986= (c.5958C>T) is associated with hereditary spherocytosis type 3, elliptocytosis 2, pyropoikilocytosis, hereditary (ClinVar).

How is Hereditary spherocytosis inherited?

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

SPTA1 p.Pro1986=

Q: How common is SPTA1 p.Pro1986= (c.5958C>T) in the general population?

SPTA1 p.Pro1986= (c.5958C>T) is common (popmax 43.1%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.5958C>T · rs3753068 · VCV258949

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Common

common (popmax 43.1%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

hereditary spherocytosis type 3

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 -5	GERP -3.5
Overall
CADD	0.557	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 43.1% African / African-American · 32,257/74,870 alleles

Filtering AF 42.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 42.5%

Overall 30% 483,907/1,613,570 alleles · common exomes 433,639/1,461,702 · genomes 50,268/151,868 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	43.1%	2
Ashkenazi Jewishnot grpmax-eligible	40.1%	2
Middle Eastern	33.9%	3
Finnishnot grpmax-eligible	30.2%	3
Remaining individualsnot grpmax-eligible	30.1%	3
South Asian	30%	3
European (non-Finnish)	29.7%	3
Amishnot grpmax-eligible	22.7%	4
Admixed American	21.7%	5
East Asian	20.1%	5

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.Pro1986=
Coding: c.5958C>T
MANE Select: NM_003126
dbSNP: rs3753068
Type: single nucleotide variant
Location: chr1:158623145 (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

hereditary spherocytosis type 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: elliptocytosis 2 pyropoikilocytosis, hereditary

For Hereditary spherocytosis (Orphanet):

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

Similar variants

SPTA1 p.Pro1986Leu 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-pro1986 (accessed [today's date]).

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