Is ATL1 p.Ala73Val (c.218C>T) pathogenic?

ATL1 p.Ala73Val (c.218C>T) is classified Uncertain significance in ATL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-12). AlphaMissense: likely pathogenic (0.9455); Absent from gnomAD v4.1; Associated with ATL1-related disorder.

What condition is associated with ATL1 p.Ala73Val (c.218C>T)?

ATL1 p.Ala73Val (c.218C>T) is associated with ATL1-related disorder (ClinVar).

How common is ATL1 p.Ala73Val (c.218C>T) in the general population?

ATL1 p.Ala73Val (c.218C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ATL1 p.Ala73Val (c.218C>T)?

AlphaMissense predicts likely pathogenic (score 0.9455) — an in-silico prediction, not a clinical call.

ATL1 p.Ala73Val

c.218C>T · rs951568761 · VCV2633006

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9455 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

ATL1-related disorder

Computational evidence

Protein change
AlphaMissense	0.9455	likely pathogenic
REVEL	0.465	indeterminate
SaProt	LLR -9.80	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 31 kb · p 0.00045 · regional, not allelic
Overall
CADD	26.4	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ATL1
Protein: p.Ala73Val
Coding: c.218C>T
MANE Select: NM_015915
dbSNP: rs951568761
Type: single nucleotide variant
Location: chr14:50588014 (GRCh38)
Gene constraint: LOEUF 0.57 · pLI 0.36 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 86.49 · 14 PDB
Residue 73: 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

ATL1-related disorder

Similar variants

ATL1 p.Arg217Gln Pathogenic/Likely pathogenic ★★ same condition
ATL1 p.Arg239Cys Pathogenic/Likely pathogenic ★★ same condition
ATL1 p.Arg415Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
ATL1 p.Arg416Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
ATL1 p.Arg501Ter Pathogenic ★★ same condition
ATL1 p.Leu357Ser Uncertain significance ★★ ⚠ same condition
ATL1 p.Asn252Lys Conflicting classifications of pathogenicity ★ ⚠ same condition
ATL1 p.His343Asp Conflicting classifications of pathogenicity ★ ⚠ 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-ala73val (accessed [today's date]).

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