Is ATM p.Phe1209= (c.3627T>C) pathogenic?

ATM p.Phe1209= (c.3627T>C) is classified Benign/Likely benign in ATM (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-10-25). Very rare (popmax 0.0067%, eas); Associated with hereditary neoplastic syndrome.

What condition is associated with ATM p.Phe1209= (c.3627T>C)?

ATM p.Phe1209= (c.3627T>C) is associated with hereditary neoplastic syndrome, ataxia telangiectasia, hereditary breast carcinoma (ClinVar).

How common is ATM p.Phe1209= (c.3627T>C) in the general population?

ATM p.Phe1209= (c.3627T>C) is very rare (popmax 0.0067%, eas) (gnomAD).

ATM p.Phe1209=

c.3627T>C · rs762605020 · VCV220120

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0067%, eas)

Conditions

hereditary neoplastic syndrome

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 0.41	GERP -2, phastCons 0.99
Overall
CADD	8.532	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0067% East Asian · 3/44,770 alleles

Filtering AF 0.00178% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000893%

Overall 0.000496% 8/1,612,940 alleles · very rare exomes 7/1,460,716 · genomes 1/152,224 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0067%	14,923
European (non-Finnish)	0.000424%	235,855

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.Phe1209=
Coding: c.3627T>C
MANE Select: NM_000051
dbSNP: rs762605020
Type: single nucleotide variant
Location: chr11:108282760 (GRCh38)
Gene constraint: LOEUF 0.847 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 1209: a UniProt-annotated variant site (in at); an α-helix; 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

Also linked: ataxia telangiectasia hereditary breast carcinoma

Similar variants

ATM p.Phe1209Ile Uncertain significance ★★ same residue
ATM p.Phe1209Val Uncertain significance ★ same residue
ATM p.Phe1209_Met1210delinsSerHisTer Pathogenic ★ same residue
ATM p.Phe1209fs 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

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-phe1209 (accessed [today's date]).

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