Is ATM p.Ser2000Ile (c.5999G>T) pathogenic?

ATM p.Ser2000Ile (c.5999G>T) is classified Uncertain significance in ATM (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-11-17). AlphaMissense: likely benign (0.2323); Ultra-rare (popmax 0.0168%, mid); Associated with hereditary neoplastic syndrome.

What condition is associated with ATM p.Ser2000Ile (c.5999G>T)?

ATM p.Ser2000Ile (c.5999G>T) is associated with hereditary neoplastic syndrome, ataxia telangiectasia (ClinVar).

How common is ATM p.Ser2000Ile (c.5999G>T) in the general population?

ATM p.Ser2000Ile (c.5999G>T) is ultra-rare (popmax 0.0168%, mid) (gnomAD).

What do computational predictors say about ATM p.Ser2000Ile (c.5999G>T)?

AlphaMissense predicts likely benign (score 0.2323) — an in-silico prediction, not a clinical call.

ATM p.Ser2000Ile

c.5999G>T · rs775921052 · VCV964752

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.2323 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0168%, mid)

Conditions

hereditary neoplastic syndrome

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.2323	likely benign
REVEL	0.334	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 9.8	GERP 2.5, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 60 kb · p 6.4e-07 · regional, not allelic
Overall
CADD	25.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0168% Middle Eastern · 1/5,942 alleles

Overall 6.41e-05% 1/1,561,198 alleles · ultra-rare exomes 1/1,408,906 · genomes 0/152,292 · joint denominator

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: ATM
Protein: p.Ser2000Ile
Coding: c.5999G>T
MANE Select: NM_000051
dbSNP: rs775921052
Type: single nucleotide variant
Location: chr11:108312491 (GRCh38)

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

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: ataxia telangiectasia

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/atm-p-ser2000ile (accessed [today's date]).

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