Is ATM p.Phe825= (c.2475C>T) pathogenic?

ATM p.Phe825= (c.2475C>T) is classified Benign/Likely benign in ATM (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-28). Very rare (popmax 0.00223%, eas); Associated with ataxia telangiectasia.

What condition is associated with ATM p.Phe825= (c.2475C>T)?

ATM p.Phe825= (c.2475C>T) is associated with ataxia telangiectasia, hereditary neoplastic syndrome, hereditary breast carcinoma (ClinVar).

How common is ATM p.Phe825= (c.2475C>T) in the general population?

ATM p.Phe825= (c.2475C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

How is Ataxia-telangiectasia inherited?

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

ATM p.Phe825=

c.2475C>T · rs776907383 · VCV507746

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

ataxia telangiectasia

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 1.2	GERP -4.7, phastCons 0.91
Overall
CADD	1.507	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,876 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000372% 6/1,613,840 alleles · very rare exomes 5/1,461,734 · genomes 1/152,106 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,876
Admixed American	0.00167%	59,990
European (non-Finnish)	0.000339%	294,992

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.Phe825=
Coding: c.2475C>T
MANE Select: NM_000051
dbSNP: rs776907383
Type: single nucleotide variant
Location: chr11:108267179 (GRCh38)
Gene constraint: LOEUF 0.847 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 825: 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

ataxia telangiectasia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome hereditary breast carcinoma

For Ataxia-telangiectasia (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy
Prevalence: 1-5 / 10 000 (Norway)

Similar variants

ATM p.Phe825Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
ATM p.Phe825Val Conflicting classifications of pathogenicity ★ ⚠ 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-phe825 (accessed [today's date]).

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