Is ATM p.Asp211Val (c.632A>T) pathogenic?

ATM p.Asp211Val (c.632A>T) is classified Uncertain significance in ATM (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-05). AlphaMissense: likely benign (0.1036); Very rare (popmax 0.00167%, amr); Associated with hereditary neoplastic syndrome.

What condition is associated with ATM p.Asp211Val (c.632A>T)?

ATM p.Asp211Val (c.632A>T) is associated with hereditary neoplastic syndrome (ClinVar).

How common is ATM p.Asp211Val (c.632A>T) in the general population?

ATM p.Asp211Val (c.632A>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about ATM p.Asp211Val (c.632A>T)?

AlphaMissense predicts likely benign (score 0.1036) — an in-silico prediction, not a clinical call.

ATM p.Asp211Val

c.632A>T · rs1387925127 · VCV628624

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1036 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.1036	likely benign
REVEL	0.116	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.2	GERP 2.3, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 66 kb · p 0.75 · regional, not allelic
Overall
CADD	19.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,990 alleles

Overall 6.84e-05% 1/1,461,570 alleles · very rare

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.Asp211Val
Coding: c.632A>T
MANE Select: NM_000051
dbSNP: rs1387925127
Type: single nucleotide variant
Location: chr11:108244088 (GRCh38)
Gene constraint: LOEUF 0.847 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 211: a UniProt-annotated variant site (in at); an α-helix

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.Asp211Asn Uncertain significance ★★ ⚠ same residue
ATM p.Asp211= Likely benign ★★ same residue
ATM p.Asp211Glu Conflicting classifications of pathogenicity ★ ⚠ 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
ATM c.332-1G>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-asp211val (accessed [today's date]).

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