Is SPTAN1 p.Asp2139= (c.6417C>T) pathogenic?

SPTAN1 p.Asp2139= (c.6417C>T) is classified Benign/Likely benign in SPTAN1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-08-18). Ultra-rare (popmax 0.0294%, afr); Associated with early-infantile DEE.

What condition is associated with SPTAN1 p.Asp2139= (c.6417C>T)?

SPTAN1 p.Asp2139= (c.6417C>T) is associated with early-infantile DEE, developmental and epileptic encephalopathy, 5 (ClinVar).

How common is SPTAN1 p.Asp2139= (c.6417C>T) in the general population?

SPTAN1 p.Asp2139= (c.6417C>T) is ultra-rare (popmax 0.0294%, afr) (gnomAD).

SPTAN1 p.Asp2139=

c.6417C>T · rs140418358 · VCV378662

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0294%, afr)

Conditions

early-infantile DEE

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 -11	GERP -4
Overall
CADD	6.392	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0294% African / African-American · 22/74,940 alleles

Filtering AF 0.0199% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0167%

Overall 0.00991% 160/1,614,058 alleles · ultra-rare exomes 136/1,461,842 · genomes 24/152,216 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.193%	519
African / African-Americangrpmax	0.0294%	3,406
Remaining individualsnot grpmax-eligible	0.0272%	3,676
Admixed American	0.02%	5,001
European (non-Finnish)	0.00398%	25,107
South Asian	0.00329%	30,363
East Asian	0.00223%	44,896
Finnishnot grpmax-eligible	0.00156%	64,012

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: SPTAN1
Protein: p.Asp2139=
Coding: c.6417C>T
MANE Select: NM_001130438
dbSNP: rs140418358
Type: single nucleotide variant
Location: chr9:128626528 (GRCh38)
Gene constraint: LOEUF 0.222 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.05 · 7 PDB
Residue 2139: a UniProt-annotated variant site (in hmnd11; pathogenic; decreased protein levels in patient cells); a UniProt-annotated variant site (in devep; likely pathogenic); a UniProt-annotated variant site (in hmnd11; likely pathogenic; decreased protein levels in patient cells)

Full SPTAN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

early-infantile DEE — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: developmental and epileptic encephalopathy, 5

Similar variants

SPTAN1 p.Asp2139Asn Uncertain significance ★ ⚠ same residue
SPTAN1 p.Asp2139Gly Uncertain significance ★ ⚠ same residue
SPTAN1 p.Arg139Ter Likely pathogenic ★★ same condition
SPTAN1 p.Arg156Ter Pathogenic/Likely pathogenic ★★ same condition
SPTAN1 p.Arg1610Trp Pathogenic/Likely pathogenic ★★ same condition
SPTAN1 p.Arg2308Cys Pathogenic/Likely pathogenic ★★ same condition
SPTAN1 p.Arg548Ter Pathogenic ★★ same condition
SPTAN1 p.Glu2271Lys 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/sptan1-p-asp2139 (accessed [today's date]).

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