Is ATM p.Pro1607= (c.4821A>G) pathogenic?

ATM p.Pro1607= (c.4821A>G) is classified Benign/Likely benign in ATM (ClinVar, Multiple submitters, 8 submitters; last evaluated 2025-09-07). Very rare (popmax 0.00195%, nfe); Associated with familial colorectal cancer type X.

What condition is associated with ATM p.Pro1607= (c.4821A>G)?

ATM p.Pro1607= (c.4821A>G) is associated with familial colorectal cancer type X, ataxia telangiectasia, hereditary neoplastic syndrome (ClinVar).

How common is ATM p.Pro1607= (c.4821A>G) in the general population?

ATM p.Pro1607= (c.4821A>G) is very rare (popmax 0.00195%, nfe) (gnomAD).

How is Familial colorectal cancer Type X inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

ATM p.Pro1607=

c.4821A>G · rs786203559 · VCV187216

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00195%, nfe)

Conditions

familial colorectal cancer type X

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.27	GERP -5
Overall
CADD	6.354	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00195% European (non-Finnish) · 23/1,179,858 alleles

Filtering AF 0.0013% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00108%

Overall 0.00143% 23/1,613,804 alleles · very rare exomes 22/1,461,584 · genomes 1/152,220 · 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.Pro1607=
Coding: c.4821A>G
MANE Select: NM_000051
dbSNP: rs786203559
Type: single nucleotide variant
Location: chr11:108294971 (GRCh38)
Gene constraint: LOEUF 0.847 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 1607: 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

familial colorectal cancer type X — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: ataxia telangiectasia hereditary neoplastic syndrome hereditary breast carcinoma

For Familial colorectal cancer Type X (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult, Elderly

Similar variants

ATM p.Pro1607Leu Uncertain significance ★★ same residue
ATM p.Pro1607Thr Uncertain significance ★★ same residue
ATM p.Pro1607Ala Uncertain significance ★ ⚠ same residue
ATM p.Pro1607Arg Uncertain significance ★ same residue
ATM p.Pro1607fs 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

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-pro1607 (accessed [today's date]).

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