Is ATM p.Ser549= (c.1647T>C) pathogenic?

ATM p.Ser549= (c.1647T>C) is classified Likely benign in ATM (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-10). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with ATM p.Ser549= (c.1647T>C)?

ATM p.Ser549= (c.1647T>C) is associated with hereditary neoplastic syndrome (ClinVar).

How common is ATM p.Ser549= (c.1647T>C) in the general population?

ATM p.Ser549= (c.1647T>C) is absent from gnomAD v4.1 (gnomAD).

ATM p.Ser549=

c.1647T>C · rs2135339826 · VCV1777178

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 · T>G here scores Δ0.26 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.031	GERP -5.4
Overall
CADD	4.398	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ATM
Protein: p.Ser549=
Coding: c.1647T>C
MANE Select: NM_000051
dbSNP: rs2135339826
Type: single nucleotide variant
Location: chr11:108251876 (GRCh38)
Gene constraint: LOEUF 0.847 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 549: a UniProt-annotated variant site (in at); 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

Similar variants

ATM p.Ser549Asn Uncertain significance ★★ ⚠ same residue
ATM p.Ser549fs Pathogenic ★ same residue
ATM p.Ser549Cys Uncertain significance ★ ⚠ same residue
ATM p.Ser549Gly Uncertain significance ★ ⚠ same residue
ATM p.Ser549Thr 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

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-ser549 (accessed [today's date]).

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