Is ATM p.Val723= (c.2169G>T) pathogenic?

ATM p.Val723= (c.2169G>T) is classified Benign/Likely benign in ATM (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-12-29). Ultra-rare (popmax 0.0166%, mid); Associated with hereditary breast carcinoma.

What condition is associated with ATM p.Val723= (c.2169G>T)?

ATM p.Val723= (c.2169G>T) is associated with hereditary breast carcinoma, ataxia telangiectasia, hereditary neoplastic syndrome (ClinVar).

How common is ATM p.Val723= (c.2169G>T) in the general population?

ATM p.Val723= (c.2169G>T) is ultra-rare (popmax 0.0166%, mid) (gnomAD).

How is Hereditary breast cancer inherited?

Typically Autosomal dominant, Multigenic/multifactorial (Orphanet). A genetic counselor can assess individual risk for a family.

ATM p.Val723=

c.2169G>T · rs878853491 · VCV236683

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0166%, mid)

Conditions

hereditary breast carcinoma

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 · G>A here scores Δ0.98 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.9	GERP 1.7, phastCons 1
Overall
CADD	6.792	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0166% Middle Eastern · 1/6,042 alleles

Overall 0.000137% 2/1,458,028 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0166%	6,042
Remaining individualsnot grpmax-eligible	0.00161%	62,264

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.Val723=
Coding: c.2169G>T
MANE Select: NM_000051
dbSNP: rs878853491
Type: single nucleotide variant
Location: chr11:108256259 (GRCh38)
Gene constraint: LOEUF 0.847 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 723: a UniProt-annotated variant site (in at); an α-helix; 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

hereditary breast carcinoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: ataxia telangiectasia hereditary neoplastic syndrome

For Hereditary breast cancer (Orphanet):

Inheritance: Autosomal dominant, Multigenic/multifactorial
Onset: Adult, Elderly

Similar variants

ATM p.Val723Ala Uncertain significance ★★ ⚠ same residue
ATM p.Val723Leu Uncertain significance ★★ same residue
ATM p.Val723Met Uncertain significance ★ ⚠ same residue
ATM p.Val723_Gly724insTer 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-val723 (accessed [today's date]).

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