Is ATM p.Asn3003Ser (c.9008A>G) pathogenic?

ATM p.Asn3003Ser (c.9008A>G) is classified Conflicting classifications of pathogenicity in ATM (ClinVar, Conflicting submitters, 9 submitters; last evaluated 2025-12-03). AlphaMissense: likely benign (0.2318); Very rare (popmax 0.000169%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with ATM p.Asn3003Ser (c.9008A>G)?

ATM p.Asn3003Ser (c.9008A>G) is associated with hereditary neoplastic syndrome, ataxia telangiectasia, hereditary breast carcinoma (ClinVar).

How common is ATM p.Asn3003Ser (c.9008A>G) in the general population?

ATM p.Asn3003Ser (c.9008A>G) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about ATM p.Asn3003Ser (c.9008A>G)?

AlphaMissense predicts likely benign (score 0.2318) — an in-silico prediction, not a clinical call.

ATM p.Asn3003Ser

c.9008A>G · rs144636562 · VCV181905

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 9 submitters

AlphaMissense

likely benign

0.2318 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.2318	likely benign
REVEL	0.33	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 359 bp · p 0.59 · regional, not allelic
Overall
CADD	24.1	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 0.000169% European (non-Finnish) · 2/1,180,022 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000205% 3/1,461,874 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,512
European (non-Finnish)grpmax	0.000169%	590,012

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asn3003Ser
Coding: c.9008A>G
MANE Select: NM_000051
dbSNP: rs144636562
Type: single nucleotide variant
Location: chr11:108365345 (GRCh38)
Gene constraint: LOEUF 0.847 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 3003: a UniProt-annotated variant site (in at; uncertain significance; reduces protein abundance); a UniProt-annotated variant site (in at); a UniProt-annotated variant site (in at; uncertain significance); a UniProt-annotated variant site (in at; decreased protein abundance); an α-helix; a UniProt-annotated variant site (in at; uncertain significance; increases protein abundance)

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 hereditary breast carcinoma

Similar variants

ATM p.Asn3003Asp Uncertain significance ★★ same residue
ATM p.Asn3003= Likely benign ★ same residue
ATM p.Asn3003fs Pathogenic/Likely pathogenic ★★ same residue
ATM c.1607+1G>T Pathogenic ★★★ same condition
ATM c.2251-4A>G Likely pathogenic ★★★ same condition
ATM c.2466+5G>C Likely pathogenic ★★★ same condition
ATM c.3078-1G>A Pathogenic ★★★ same condition
ATM c.332-1G>A Pathogenic ★★★ 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/atm-p-asn3003ser (accessed [today's date]).

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