Is ATM p.Phe662= (c.1986T>C) pathogenic?

ATM p.Phe662= (c.1986T>C) is classified Conflicting classifications of pathogenicity in ATM (ClinVar, Conflicting submitters, 29 submitters; last evaluated 2026-02-03). Ultra-rare (popmax 0.0765%, nfe); Associated with Breast and/or ovarian cancer.

What condition is associated with ATM p.Phe662= (c.1986T>C)?

ATM p.Phe662= (c.1986T>C) is associated with Breast and/or ovarian cancer, hereditary breast ovarian cancer syndrome, breast cancer (ClinVar).

How common is ATM p.Phe662= (c.1986T>C) in the general population?

ATM p.Phe662= (c.1986T>C) is ultra-rare (popmax 0.0765%, nfe) (gnomAD).

ATM p.Phe662=

c.1986T>C · rs1800055 · VCV135740

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 29 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0765%, nfe)

Conditions

Breast and/or ovarian cancer

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 3.5	GERP 1.4, phastCons 1
Overall
CADD	11.4	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0765% European (non-Finnish) · 903/1,179,982 alleles

Filtering AF 0.0723% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0707%

Overall 0.0623% 1,006/1,613,978 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.142%	705
European (non-Finnish)grpmax	0.0765%	1,307
Remaining individualsnot grpmax-eligible	0.064%	1,562
Admixed American	0.0183%	5,455
African / African-American	0.00934%	10,704
Finnishnot grpmax-eligible	0.00469%	21,343

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Phe662=
Coding: c.1986T>C
MANE Select: NM_000051
dbSNP: rs1800055
Type: single nucleotide variant
Location: chr11:108253901 (GRCh38)
Gene constraint: LOEUF 0.847 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 662: a UniProt-annotated variant site (in at); a UniProt-annotated variant site (in at; uncertain significance)

Full ATM gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Breast and/or ovarian cancer — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary breast ovarian cancer syndrome breast cancer ataxia telangiectasia hereditary neoplastic syndrome hereditary breast carcinoma

Similar variants

ATM p.Phe662Ile Likely benign ★ same residue
ATM p.Phe662_Leu663insTer 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
ATM c.332-1G>A Pathogenic ★★★ same condition
ATM c.4909+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-phe662 (accessed [today's date]).

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