Is ATRIP p.Thr766Met (c.2297C>T) pathogenic?

ATRIP p.Thr766Met (c.2297C>T) is classified Conflicting classifications of pathogenicity in ATRIP (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-02-16). AlphaMissense: likely benign (0.0928); Ultra-rare (popmax 0.0333%, nfe).

How common is ATRIP p.Thr766Met (c.2297C>T) in the general population?

ATRIP p.Thr766Met (c.2297C>T) is ultra-rare (popmax 0.0333%, nfe) (gnomAD).

What do computational predictors say about ATRIP p.Thr766Met (c.2297C>T)?

AlphaMissense predicts likely benign (score 0.0928) — an in-silico prediction, not a clinical call.

ATRIP p.Thr766Met

c.2297C>T · rs137912936 · VCV2052675

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0928 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0333%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0928	likely benign
REVEL	0.114	moderately benign-leaning
SaProt	LLR -9.91	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.41 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.8	GERP 1.5, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 19 kb · p 0.089 · regional, not allelic
Overall
CADD	23.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0333% European (non-Finnish) · 392/1,176,406 alleles

Filtering AF 0.0305% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0295%

Overall 0.027% 435/1,609,246 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0333%	3,001
Admixed American	0.0234%	4,280
Finnishnot grpmax-eligible	0.0189%	5,299
Middle Eastern	0.0165%	6,046
African / African-American	0.012%	8,327
Remaining individualsnot grpmax-eligible	0.00964%	10,378
East Asian	0.00224%	44,742

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: ATRIP
Protein: p.Thr766Met
Coding: c.2297C>T
MANE Select: NM_130384
dbSNP: rs137912936
Type: single nucleotide variant
Location: chr3:48465072 (GRCh38)
Gene constraint: LOEUF 0.707 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.10 · 24 PDB

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

Similar variants

ATRIP p.Thr766= Uncertain significance ★ same residue
ATRIP p.Thr766Pro Uncertain significance ★ ⚠ same residue
TREX1 p.Arg114His Pathogenic/Likely pathogenic ★★ ⚠ same type
TREX1 p.Arg164Ter Pathogenic/Likely pathogenic ★★ same type
TREX1 p.Asp18Asn Pathogenic ★★ same type
TREX1 p.Asp200His Likely pathogenic ★★ same type
TREX1 p.Gln135Ter Pathogenic/Likely pathogenic ★★ same type
ATRIP p.Ala119Thr Uncertain significance ★★ ⚠ same type

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/atrip-p-thr766met (accessed [today's date]).

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