Is DNTTIP2 p.Ile306Thr (c.917T>C) pathogenic?

DNTTIP2 p.Ile306Thr (c.917T>C) is classified Uncertain significance in DNTTIP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-30). AlphaMissense: likely benign (0.1774); Ultra-rare (popmax 0.032%, afr).

How common is DNTTIP2 p.Ile306Thr (c.917T>C) in the general population?

DNTTIP2 p.Ile306Thr (c.917T>C) is ultra-rare (popmax 0.032%, afr) (gnomAD).

What do computational predictors say about DNTTIP2 p.Ile306Thr (c.917T>C)?

AlphaMissense predicts likely benign (score 0.1774) — an in-silico prediction, not a clinical call.

DNTTIP2 p.Ile306Thr

c.917T>C · VCV4243723

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1774 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.032%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1774	likely benign
REVEL	0.057	moderately benign-leaning
SaProt	LLR -6.30	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.5	GERP 0.79, phastCons 0.001
Regional constraint	o/e 1.02	unconstrained · MANE · 9,294 bp · p 0.47 · regional, not allelic
Overall
CADD	15.33	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 0.032% African / African-American · 24/75,040 alleles

Filtering AF 0.022% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0187%

Overall 0.0018% 29/1,612,686 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.032%	3,127
Remaining individualsnot grpmax-eligible	0.0032%	31,235
Admixed American	0.00167%	60,012
European (non-Finnish)	0.00017%	589,890

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: DNTTIP2
Protein: p.Ile306Thr
Coding: c.917T>C
MANE Select: NM_014597
Type: single nucleotide variant
Location: chr1:93877018 (GRCh38)
Gene constraint: LOEUF 0.976 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.47 · 3 PDB

Full DNTTIP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNTTIP2 p.Ala11Thr Uncertain significance ★ ⚠ same type
DNTTIP2 p.Ala347Val Uncertain significance ★ ⚠ same type
DNTTIP2 p.Ala358Pro Uncertain significance ★ ⚠ same type
DNTTIP2 p.Ala43Ser Uncertain significance ★ ⚠ same type
DNTTIP2 p.Ala43Thr Uncertain significance ★ ⚠ same type
DNTTIP2 p.Ala43Val Uncertain significance ★ ⚠ same type
DNTTIP2 p.Ala511Val Uncertain significance ★ ⚠ same type
DNTTIP2 p.Ala554Val 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/dnttip2-p-ile306thr (accessed [today's date]).

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