Is ATL1 p.Ala69Ser (c.205G>T) pathogenic?

ATL1 p.Ala69Ser (c.205G>T) is classified Uncertain significance in ATL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-28). AlphaMissense: ambiguous (0.4002); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ATL1 p.Ala69Ser (c.205G>T)?

ATL1 p.Ala69Ser (c.205G>T) is associated with Inborn genetic diseases (ClinVar).

How common is ATL1 p.Ala69Ser (c.205G>T) in the general population?

ATL1 p.Ala69Ser (c.205G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ATL1 p.Ala69Ser (c.205G>T)?

AlphaMissense predicts ambiguous (score 0.4002) — an in-silico prediction, not a clinical call.

ATL1 p.Ala69Ser

c.205G>T · VCV3797633

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4002 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4002	ambiguous
REVEL	0.423	indeterminate
SaProt	LLR -7.77	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 1.8, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 31 kb · p 0.00045 · regional, not allelic
Overall
CADD	25.7	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.Ala69Ser
Coding: c.205G>T
MANE Select: NM_015915
Type: single nucleotide variant
Location: chr14:50588001 (GRCh38)
Gene constraint: LOEUF 0.57 · pLI 0.36 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 86.49 · 14 PDB
Residue 69: 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

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

Similar variants

ATL1 p.Ala69Val Uncertain significance ★★ ⚠ same residue
ATL1 p.Lys407Met Pathogenic/Likely pathogenic ★★ same condition
ATL1 c.630+3G>A Uncertain significance ★★ same condition
ATL1 p.Ala200Thr Uncertain significance ★★ ⚠ same condition
ATL1 p.Ala229Gly Uncertain significance ★★ ⚠ same condition
ATL1 p.Arg323Gln Uncertain significance ★★ ⚠ same condition
ATL1 p.Asn263Ser Uncertain significance ★★ ⚠ same condition
ATL1 p.Asn318Ile Uncertain significance ★★ ⚠ 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-ala69ser (accessed [today's date]).

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