Is ATR p.Thr1663Ile (c.4988C>T) pathogenic?

ATR p.Thr1663Ile (c.4988C>T) is classified Uncertain significance in ATR (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-23). AlphaMissense: likely benign (0.0703); Very rare (popmax 0.00401%, afr); Associated with Inborn genetic diseases.

What condition is associated with ATR p.Thr1663Ile (c.4988C>T)?

ATR p.Thr1663Ile (c.4988C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ATR p.Thr1663Ile (c.4988C>T) in the general population?

ATR p.Thr1663Ile (c.4988C>T) is very rare (popmax 0.00401%, afr) (gnomAD).

What do computational predictors say about ATR p.Thr1663Ile (c.4988C>T)?

AlphaMissense predicts likely benign (score 0.0703) — an in-silico prediction, not a clinical call.

ATR p.Thr1663Ile

c.4988C>T · rs984341860 · VCV1744554

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0703 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0703	likely benign
REVEL	0.036	moderately benign-leaning
SaProt	LLR -6.74	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.26	donor loss, 43 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 4.5	GERP 0.82, phastCons 1
Overall
CADD	16.99	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 and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00401% African / African-American · 3/74,764 alleles

Filtering AF 0.00107% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000248% 4/1,613,144 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,921
Remaining individualsnot grpmax-eligible	0.0016%	62,468

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: ATR
Protein: p.Thr1663Ile
Coding: c.4988C>T
MANE Select: NM_032208 · reported on NM_001184
dbSNP: rs984341860
Type: single nucleotide variant
Location: chr3:142507974 (GRCh38)
Structure: AlphaFold pLDDT 72.76 · 5 PDB

Full ATR gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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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/atr-p-thr1663ile (accessed [today's date]).

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