Is ATL1 p.Val360Met (c.1078G>A) pathogenic?

ATL1 p.Val360Met (c.1078G>A) is classified Conflicting classifications of pathogenicity in ATL1 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-12-29). AlphaMissense: likely pathogenic (0.5809); Very rare (popmax 0.00267%, afr); Associated with Inborn genetic diseases.

What condition is associated with ATL1 p.Val360Met (c.1078G>A)?

ATL1 p.Val360Met (c.1078G>A) is associated with Inborn genetic diseases, hereditary spastic paraplegia 3A (ClinVar).

How common is ATL1 p.Val360Met (c.1078G>A) in the general population?

ATL1 p.Val360Met (c.1078G>A) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about ATL1 p.Val360Met (c.1078G>A)?

AlphaMissense predicts likely pathogenic (score 0.5809) — an in-silico prediction, not a clinical call.

ATL1 p.Val360Met

c.1078G>A · rs373267047 · VCV390443

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.5809 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5809	likely pathogenic
REVEL	0.427	indeterminate
SaProt	LLR -10.80	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.67	unconstrained · MANE · 9,131 bp · p 2.1e-07 · regional, not allelic
Overall
CADD	27.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,910 alleles

Filtering AF 0.00145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00123%

Overall 0.0018% 29/1,613,800 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,455
European (non-Finnish)	0.00212%	47,196
Admixed American	0.00167%	59,994
Finnishnot grpmax-eligible	0.00156%	64,016

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.Val360Met
Coding: c.1078G>A
MANE Select: NM_015915
dbSNP: rs373267047
Type: single nucleotide variant
Location: chr14:50623207 (GRCh38)
Gene constraint: LOEUF 0.57 · pLI 0.36 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 86.49 · 14 PDB
Residue 360: an α-helix; the '3hb (three-helix bundle) domain' region

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

Similar variants

ATL1 p.Val360Gly Uncertain significance ★ ⚠ same residue
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

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-val360met (accessed [today's date]).

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