Is ATL1 p.Lys207= (c.621G>A) pathogenic?

ATL1 p.Lys207= (c.621G>A) is classified Benign/Likely benign in ATL1 (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-06-01). Rare (popmax 0.803%, afr); Associated with Inborn genetic diseases.

What condition is associated with ATL1 p.Lys207= (c.621G>A)?

ATL1 p.Lys207= (c.621G>A) is associated with Inborn genetic diseases, hereditary spastic paraplegia 3A, neuropathy, hereditary sensory, type 1D (ClinVar).

How common is ATL1 p.Lys207= (c.621G>A) in the general population?

ATL1 p.Lys207= (c.621G>A) is rare (popmax 0.803%, afr) (gnomAD).

ATL1 p.Lys207=

c.621G>A · rs35629585 · VCV21533

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

gnomAD v4.1

Rare

rare (popmax 0.803%, afr)

Conditions

Inborn genetic diseases

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 3.3	GERP -2.8, phastCons 1
Overall
CADD	9.461	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.803% African / African-American · 602/74,932 alleles

Filtering AF 0.75% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.729%

Overall 0.0442% 714/1,613,716 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.803%	124
Admixed American	0.0867%	1,154
Middle Eastern	0.0826%	1,211
Remaining individualsnot grpmax-eligible	0.0576%	1,736
South Asian	0.00549%	18,213
European (non-Finnish)	0.00119%	84,279

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.Lys207=
Coding: c.621G>A
MANE Select: NM_015915
dbSNP: rs35629585
Type: single nucleotide variant
Location: chr14:50595623 (GRCh38)
Gene constraint: LOEUF 0.57 · pLI 0.36 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 86.49 · 14 PDB
Residue 207: the gb1/rhd3-type g domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary spastic paraplegia 3A neuropathy, hereditary sensory, type 1D hereditary spastic paraplegia

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-lys207 (accessed [today's date]).

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