Is ATM p.Ser169= (c.507T>C) pathogenic?

ATM p.Ser169= (c.507T>C) is classified Conflicting classifications of pathogenicity in ATM (ClinVar, Conflicting submitters, 17 submitters; last evaluated 2025-12-17). Ultra-rare (popmax 0.0332%, mid); Associated with familial colorectal cancer type X.

What condition is associated with ATM p.Ser169= (c.507T>C)?

ATM p.Ser169= (c.507T>C) is associated with familial colorectal cancer type X, ataxia telangiectasia, hereditary neoplastic syndrome (ClinVar).

How common is ATM p.Ser169= (c.507T>C) in the general population?

ATM p.Ser169= (c.507T>C) is ultra-rare (popmax 0.0332%, mid) (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.Ser169=

c.507T>C · rs758619186 · VCV184009

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 17 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0332%, mid)

Conditions

familial colorectal cancer type X

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.51	acceptor loss, 12 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 1.5	GERP -3.2, phastCons 1
Overall
CADD	9.411	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0332% Middle Eastern · 2/6,022 alleles

Filtering AF 0.00585% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00243%

Overall 0.00132% 21/1,587,992 alleles · ultra-rare exomes 18/1,435,994 · genomes 3/151,998 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0332%	3,011
European (non-Finnish)	0.00163%	61,325

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.Ser169=
Coding: c.507T>C
MANE Select: NM_000051
dbSNP: rs758619186
Type: single nucleotide variant
Location: chr11:108243963 (GRCh38)
Gene constraint: LOEUF 0.847 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 169: a UniProt-annotated variant site (in at); an α-helix

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.Ser169Cys Uncertain significance ★★ ⚠ same residue
ATM p.Ser169Phe Uncertain significance ★★ ⚠ same residue
ATM p.Ser169fs Pathogenic ★ same residue
ATM p.Ser169_Phe172del 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
ATM c.3078-1G>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-ser169 (accessed [today's date]).

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