Is ATM p.Pro1639= (c.4917G>C) pathogenic?

ATM p.Pro1639= (c.4917G>C) is classified Likely benign in ATM (ClinVar, Single submitter, 1 submitter; last evaluated 2020-03-16). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with ATM p.Pro1639= (c.4917G>C)?

ATM p.Pro1639= (c.4917G>C) is associated with hereditary neoplastic syndrome (ClinVar).

How common is ATM p.Pro1639= (c.4917G>C) in the general population?

ATM p.Pro1639= (c.4917G>C) is absent from gnomAD v4.1 (gnomAD).

ATM p.Pro1639=

c.4917G>C · rs140425622 · VCV1744085

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.30	acceptor loss, 7 bp away · masked 0 · deltas
Pangolin	Δ0.26	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 0.097	GERP -4.4, phastCons 0.16
Overall
CADD	0.298	PHRED · no single calibrated threshold — expert panels disagree

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.Pro1639=
Coding: c.4917G>C
MANE Select: NM_000051
dbSNP: rs140425622
Type: single nucleotide variant
Location: chr11:108297294 (GRCh38)
Gene constraint: LOEUF 0.847 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 1639: a UniProt-annotated variant site (in at); a UniProt-annotated variant site (in at; uncertain significance); 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

Similar variants

ATM p.Pro1639Arg Uncertain significance ★★ same residue
ATM p.Pro1639Ala Uncertain significance ★ ⚠ same residue
ATM p.Pro1639Leu Conflicting classifications of pathogenicity ★ same residue
ATM p.Pro1639fs Pathogenic ★ same residue
ATM p.Pro1639Ser Uncertain significance ★ ⚠ same residue
ATM p.Pro1639Thr Uncertain significance ★ same residue
ATM c.1607+1G>T Pathogenic ★★★ same condition
ATM c.2251-4A>G 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-pro1639 (accessed [today's date]).

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