Is ATM p.Pro2829Ala (c.8485C>G) pathogenic?

ATM p.Pro2829Ala (c.8485C>G) is classified Uncertain significance in ATM (ClinVar, Single submitter, 1 submitter; last evaluated 2026-06-11). AlphaMissense: likely pathogenic (0.7898); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with ATM p.Pro2829Ala (c.8485C>G)?

ATM p.Pro2829Ala (c.8485C>G) is associated with hereditary neoplastic syndrome (ClinVar).

How common is ATM p.Pro2829Ala (c.8485C>G) in the general population?

ATM p.Pro2829Ala (c.8485C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ATM p.Pro2829Ala (c.8485C>G)?

AlphaMissense predicts likely pathogenic (score 0.7898) — an in-silico prediction, not a clinical call.

ATM p.Pro2829Ala

c.8485C>G · VCV4867106

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7898 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.7898	likely pathogenic
REVEL	0.852	moderately pathogenic-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this damaging; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.8, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 60 kb · p 6.4e-07 · regional, not allelic
Overall
CADD	25.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

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: ATM
Protein: p.Pro2829Ala
Coding: c.8485C>G
MANE Select: NM_000051
Type: single nucleotide variant
Location: chr11:108345809 (GRCh38)
Gene constraint: LOEUF 0.847 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 2829: a UniProt-annotated variant site (in at; uncertain significance; reduces protein abundance); a UniProt-annotated variant site (in at); the pi3k/pi4k catalytic domain; a UniProt-annotated variant site (in at; uncertain significance); 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

Similar variants

ATM p.Pro2829Leu Likely pathogenic ★★★ same residue
ATM p.Pro2829Arg Uncertain significance ★★ ⚠ same residue
ATM p.Pro2829Ser Likely pathogenic ★ same residue
ATM p.Pro2829Gln Uncertain significance ★ ⚠ same residue
ATM p.Pro2829Thr Uncertain significance ★ ⚠ 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

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-pro2829ala (accessed [today's date]).

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