Is ATL1 p.Asp136= (c.408T>C) pathogenic?

ATL1 p.Asp136= (c.408T>C) is classified Benign/Likely benign in ATL1 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-04-01). Low-frequency (popmax 1.41%, eas); Associated with neuropathy, hereditary sensory, type 1D.

What condition is associated with ATL1 p.Asp136= (c.408T>C)?

ATL1 p.Asp136= (c.408T>C) is associated with neuropathy, hereditary sensory, type 1D, hereditary spastic paraplegia 3A, hereditary spastic paraplegia (ClinVar).

How common is ATL1 p.Asp136= (c.408T>C) in the general population?

ATL1 p.Asp136= (c.408T>C) is low-frequency (popmax 1.41%, eas) (gnomAD).

ATL1 p.Asp136=

Q: How is Hereditary sensory and autonomic neuropathy type 1 inherited?

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

c.408T>C · rs76375909 · VCV313293

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.41%, eas)

Conditions

neuropathy, hereditary sensory, type 1D

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.73 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.47	GERP 0.58, phastCons 1
Overall
CADD	9.837	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.41% East Asian · 634/44,834 alleles

Filtering AF 1.32% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.29%

Overall 0.0426% 688/1,613,430 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	1.41%	71
Remaining individualsnot grpmax-eligible	0.0624%	1,602
African / African-American	0.0107%	9,381
Admixed American	0.00667%	15,002
South Asian	0.0022%	45,526
European (non-Finnish)	8.48e-05%	1,179,727

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: ATL1
Protein: p.Asp136=
Coding: c.408T>C
MANE Select: NM_015915
dbSNP: rs76375909
Type: single nucleotide variant
Location: chr14:50591066 (GRCh38)
Gene constraint: LOEUF 0.57 · pLI 0.36 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 86.49 · 14 PDB
Residue 136: the gb1/rhd3-type g domain; a β-strand

Full ATL1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

neuropathy, hereditary sensory, type 1D — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary spastic paraplegia 3A hereditary spastic paraplegia

For Hereditary sensory and autonomic neuropathy type 1 (Orphanet):

Inheritance: Autosomal dominant
Onset: All ages

Similar variants

ATL1 p.Arg217Gln Pathogenic/Likely pathogenic ★★ same condition
ATL1 p.Arg239Cys Pathogenic/Likely pathogenic ★★ same condition
ATL1 p.Arg239His Likely pathogenic ★★ same condition
ATL1 p.Arg403Pro Likely pathogenic ★★ same condition
ATL1 p.Arg415Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
ATL1 p.Arg416Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
ATL1 p.Arg495Trp Pathogenic/Likely pathogenic ★★ same condition
ATL1 p.Gly409Cys 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/atl1-p-asp136 (accessed [today's date]).

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