Is ATL2 p.Asp319Val (c.956A>T) pathogenic?

ATL2 p.Asp319Val (c.956A>T) is classified Uncertain significance in ATL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-25). AlphaMissense: likely benign (0.3274); Very rare (popmax 0.00884%, sas).

How common is ATL2 p.Asp319Val (c.956A>T) in the general population?

ATL2 p.Asp319Val (c.956A>T) is very rare (popmax 0.00884%, sas) (gnomAD).

What do computational predictors say about ATL2 p.Asp319Val (c.956A>T)?

AlphaMissense predicts likely benign (score 0.3274) — an in-silico prediction, not a clinical call.

ATL2 p.Asp319Val

c.956A>T · VCV4164939

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3274 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00884%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3274	likely benign
REVEL	0.701	pathogenic-leaning
SaProt	LLR -7.73	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 81 kb · p 0.18 · regional, not allelic
Overall
CADD	25.6	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 0.00884% South Asian · 8/90,532 alleles

Filtering AF 0.00439% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00314%

Overall 0.000497% 8/1,610,058 alleles · very rare

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: ATL2
Protein: p.Asp319Val
Coding: c.956A>T
MANE Select: NM_001135673
Type: single nucleotide variant
Location: chr2:38309494 (GRCh38)
Gene constraint: LOEUF 0.647 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.36
Residue 319: the gb1/rhd3-type g domain

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-asp319val (accessed [today's date]).

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