Is ATM p.Pro292= (c.876G>A) pathogenic?

ATM p.Pro292= (c.876G>A) is classified Benign/Likely benign in ATM (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-04). Very rare (popmax 0.00834%, amr); Associated with hereditary neoplastic syndrome.

What condition is associated with ATM p.Pro292= (c.876G>A)?

ATM p.Pro292= (c.876G>A) is associated with hereditary neoplastic syndrome, ataxia telangiectasia, hereditary breast carcinoma (ClinVar).

How common is ATM p.Pro292= (c.876G>A) in the general population?

ATM p.Pro292= (c.876G>A) is very rare (popmax 0.00834%, amr) (gnomAD).

ATM p.Pro292=

c.876G>A · rs755860432 · VCV230005

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00834%, amr)

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 1	GERP -3.1, phastCons 0.99
Overall
CADD	11.73	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00834% Admixed American · 5/59,950 alleles

Filtering AF 0.00324% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.00205% 33/1,610,766 alleles · very rare exomes 32/1,458,694 · genomes 1/152,072 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0439%	2,276
Admixed Americangrpmax	0.00834%	11,990
South Asian	0.00549%	18,211
Remaining individualsnot grpmax-eligible	0.00481%	20,802
African / African-American	0.00134%	74,850
European (non-Finnish)	0.000509%	196,558

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.Pro292=
Coding: c.876G>A
MANE Select: NM_000051
dbSNP: rs755860432
Type: single nucleotide variant
Location: chr11:108245001 (GRCh38)
Gene constraint: LOEUF 0.847 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 292: a UniProt-annotated variant site (in at); an α-helix; a UniProt-annotated variant site (in at; decrease phosphorylation of target proteins; increases protein abundance)

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.Pro292Leu Likely pathogenic ★★★ same residue
ATM p.Pro292Arg Uncertain significance ★★ ⚠ same residue
ATM p.Pro292Ser Uncertain significance ★ same residue
ATM p.Pro292Thr Uncertain significance ★ same residue
ATM p.Pro292fs 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

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-pro292 (accessed [today's date]).

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