Is ATM p.Val716= (c.2148C>G) pathogenic?

ATM p.Val716= (c.2148C>G) is classified Benign/Likely benign in ATM (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-01-24). Ultra-rare (popmax 0.0166%, mid); Associated with hereditary neoplastic syndrome.

What condition is associated with ATM p.Val716= (c.2148C>G)?

ATM p.Val716= (c.2148C>G) is associated with hereditary neoplastic syndrome, ataxia telangiectasia, hereditary breast carcinoma (ClinVar).

How common is ATM p.Val716= (c.2148C>G) in the general population?

ATM p.Val716= (c.2148C>G) is ultra-rare (popmax 0.0166%, mid) (gnomAD).

ATM p.Val716=

c.2148C>G · rs1800701 · VCV185153

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0166%, mid)

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 0.11	GERP -1.9, phastCons 0.93
Overall
CADD	3.986	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0166% Middle Eastern · 1/6,034 alleles

Filtering AF 8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000373% 6/1,607,628 alleles · ultra-rare exomes 6/1,455,542 · genomes 0/152,086 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0166%	6,034
Remaining individualsnot grpmax-eligible	0.00161%	62,116
European (non-Finnish)	0.00034%	293,986

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.Val716=
Coding: c.2148C>G
MANE Select: NM_000051
dbSNP: rs1800701
Type: single nucleotide variant
Location: chr11:108256238 (GRCh38)
Gene constraint: LOEUF 0.847 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 716: 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 neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: ataxia telangiectasia hereditary breast carcinoma

Similar variants

ATM p.Val716Ala Uncertain significance ★★ same residue
ATM p.Val716Asp Conflicting classifications of pathogenicity ★ ⚠ same residue
ATM p.Val716Gly Uncertain significance ★ same residue
ATM p.Val716Ile 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-val716 (accessed [today's date]).

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