Is ATL2 p.Ser35Pro (c.103T>C) pathogenic?

ATL2 p.Ser35Pro (c.103T>C) is classified Uncertain significance in ATL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-10). AlphaMissense: likely benign (0.0653); Absent from gnomAD v4.1.

How common is ATL2 p.Ser35Pro (c.103T>C) in the general population?

ATL2 p.Ser35Pro (c.103T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ATL2 p.Ser35Pro (c.103T>C)?

AlphaMissense predicts likely benign (score 0.0653) — an in-silico prediction, not a clinical call.

ATL2 p.Ser35Pro

c.103T>C · VCV4165018

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0653 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0653	likely benign
REVEL	0.145	moderately benign-leaning
SaProt	LLR -8.01	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7	GERP 1.6, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 81 kb · p 0.18 · regional, not allelic
Overall
CADD	22.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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: ATL2
Protein: p.Ser35Pro
Coding: c.103T>C
MANE Select: NM_001135673
Type: single nucleotide variant
Location: chr2:38377158 (GRCh38)
Gene constraint: LOEUF 0.647 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.36
Residue 35: the 'n-terminal hypervariable region (hvr)' region; the 'disordered' region

Full ATL2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ATL2 p.Gly365= Benign ★★ same type
ATL2 p.Ala100Val Uncertain significance ★ ⚠ same type
ATL2 p.Ala227Gly Uncertain significance ★ ⚠ same type
ATL2 p.Ala28Gly Uncertain significance ★ ⚠ same type
ATL2 p.Ala2Val Uncertain significance ★ ⚠ same type
ATL2 p.Ala388Ser Uncertain significance ★ ⚠ same type
ATL2 p.Ala388Val Uncertain significance ★ ⚠ same type
ATL2 p.Ala425Val Uncertain significance ★ ⚠ same type

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/atl2-p-ser35pro (accessed [today's date]).

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