Is ATL2 p.Pro334Ser (c.1000C>T) pathogenic?

ATL2 p.Pro334Ser (c.1000C>T) is classified Uncertain significance in ATL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-27). AlphaMissense: likely benign (0.3282); Ultra-rare (popmax 0.0241%, afr).

How common is ATL2 p.Pro334Ser (c.1000C>T) in the general population?

ATL2 p.Pro334Ser (c.1000C>T) is ultra-rare (popmax 0.0241%, afr) (gnomAD).

What do computational predictors say about ATL2 p.Pro334Ser (c.1000C>T)?

AlphaMissense predicts likely benign (score 0.3282) — an in-silico prediction, not a clinical call.

ATL2 p.Pro334Ser

c.1000C>T · rs371444918 · VCV2347713

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3282 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0241%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3282	likely benign
REVEL	0.537	indeterminate
SaProt	LLR -10.48	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 81 kb · p 0.18 · regional, not allelic
Overall
CADD	26.7	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

Grpmax group 0.0241% African / African-American · 18/74,752 alleles

Filtering AF 0.0155% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0129%

Overall 0.00155% 25/1,612,232 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0241%	4,153
Admixed American	0.00668%	14,980
Remaining individualsnot grpmax-eligible	0.0032%	31,222
East Asian	0.00223%	44,778

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.Pro334Ser
Coding: c.1000C>T
MANE Select: NM_001135673
dbSNP: rs371444918
Type: single nucleotide variant
Location: chr2:38309450 (GRCh38)
Gene constraint: LOEUF 0.647 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.36
Residue 334: 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-pro334ser (accessed [today's date]).

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