Is ATL3 p.Ser168Phe (c.503C>T) pathogenic?

ATL3 p.Ser168Phe (c.503C>T) is classified Uncertain significance in ATL3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-22). AlphaMissense: likely pathogenic (0.9983); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ATL3 p.Ser168Phe (c.503C>T)?

ATL3 p.Ser168Phe (c.503C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ATL3 p.Ser168Phe (c.503C>T) in the general population?

ATL3 p.Ser168Phe (c.503C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ATL3 p.Ser168Phe (c.503C>T)?

AlphaMissense predicts likely pathogenic (score 0.9983) — an in-silico prediction, not a clinical call.

ATL3 p.Ser168Phe

c.503C>T · VCV3444465

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9983 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9983	likely pathogenic · top 4% in ATL3
REVEL	0.96	strongly pathogenic-leaning
SaProt	LLR -17.71	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 42 kb · p 0.12 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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: ATL3
Protein: p.Ser168Phe
Coding: c.503C>T
MANE Select: NM_015459
Type: single nucleotide variant
Location: chr11:63652478 (GRCh38)
Gene constraint: LOEUF 0.891 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.30 · 2 PDB
Residue 168: a β-strand; the gb1/rhd3-type g domain

Full ATL3 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

ATL3 c.46+1G>A Uncertain significance ★★ same condition
ATL3 c.850+5G>A Uncertain significance ★★ same condition
ATL3 p.Ala540Ser Uncertain significance ★★ ⚠ same condition
ATL3 p.Ala8Thr Uncertain significance ★★ ⚠ same condition
ATL3 p.Arg194Leu Uncertain significance ★★ ⚠ same condition
ATL3 p.Arg497Cys Uncertain significance ★★ ⚠ same condition
ATL3 p.Asp259Asn Uncertain significance ★★ ⚠ same condition
ATL3 p.Asp78Gly 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/atl3-p-ser168phe (accessed [today's date]).

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