Is ATM p.Phe168= (c.504C>T) pathogenic?

ATM p.Phe168= (c.504C>T) is classified Benign/Likely benign in ATM (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-10-12). Very rare (popmax 0.0094%, eas); Associated with hereditary neoplastic syndrome.

What condition is associated with ATM p.Phe168= (c.504C>T)?

ATM p.Phe168= (c.504C>T) is associated with hereditary neoplastic syndrome, ataxia telangiectasia, hereditary breast carcinoma (ClinVar).

How common is ATM p.Phe168= (c.504C>T) in the general population?

ATM p.Phe168= (c.504C>T) is very rare (popmax 0.0094%, eas) (gnomAD).

ATM p.Phe168=

c.504C>T · rs1060504312 · VCV414611

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0094%, eas)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.37 · evaluated, not missing
Pangolin	Δ0.22	loss · gain 0.21 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP -0.66	GERP -2.1, phastCons 0.01
Overall
CADD	9.278	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0094% East Asian · 4/42,554 alleles

Filtering AF 0.00319% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00187%

Overall 0.00175% 27/1,543,852 alleles · very rare exomes 27/1,400,782 · genomes 0/143,070 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0094%	10,639
South Asian	0.00364%	27,469
Remaining individualsnot grpmax-eligible	0.00335%	29,833
Finnishnot grpmax-eligible	0.00168%	59,514
European (non-Finnish)	0.00148%	67,405

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.Phe168=
Coding: c.504C>T
MANE Select: NM_000051
dbSNP: rs1060504312
Type: single nucleotide variant
Location: chr11:108243960 (GRCh38)
Gene constraint: LOEUF 0.847 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 168: 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

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.Phe168Leu Uncertain significance ★★ ⚠ same residue
ATM p.Phe168Tyr Likely benign ★ same residue
ATM p.Phe168fs Pathogenic ★ same residue
ATM p.Phe168Ser 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-phe168 (accessed [today's date]).

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