Is ATM p.Pro178fs (c.531dup) pathogenic?

ATM p.Pro178fs (c.531dup) is classified Pathogenic in ATM (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-09-27). No gnomAD frequency available for this variant; Associated with hereditary neoplastic syndrome.

What condition is associated with ATM p.Pro178fs (c.531dup)?

ATM p.Pro178fs (c.531dup) is associated with hereditary neoplastic syndrome, hereditary breast carcinoma (ClinVar).

How common is ATM p.Pro178fs (c.531dup) in the general population?

ATM p.Pro178fs (c.531dup) is no gnomAD frequency available for this variant (gnomAD).

ATM p.Pro178fs

c.531dup · rs2497129696 · VCV1746812

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 6 of 63
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.41	GERP -1.4, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ATM
Protein: p.Pro178fs
Coding: c.531dup
MANE Select: NM_000051
dbSNP: rs2497129696
Type: Duplication
Location: chr11:108243984 (GRCh38)
Gene constraint: LOEUF 0.847 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 178: a UniProt-annotated variant site (in at)

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: hereditary breast carcinoma

Similar variants

ATM p.Pro178Leu Uncertain significance ★★ ⚠ same residue
ATM p.Pro178Ser Uncertain significance ★★ ⚠ same residue
ATM p.Pro178Thr Uncertain significance ★★ ⚠ same residue
ATM p.Pro178= Benign/Likely benign ★★ same residue
ATM p.Pro178Arg Uncertain significance ★ ⚠ same residue
ATM c.6997dup Pathogenic ★★★ same condition
ATM p.Cys718fs Pathogenic ★★★ same condition
ATM p.Ser837fs 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-pro178fs (accessed [today's date]).

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