Is DNAI2 p.Asp385Tyr (c.1153G>T) pathogenic?

DNAI2 p.Asp385Tyr (c.1153G>T) is classified Uncertain significance in DNAI2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-09). AlphaMissense: likely pathogenic (0.9243); Very rare (popmax 0.005%, amr).

How common is DNAI2 p.Asp385Tyr (c.1153G>T) in the general population?

DNAI2 p.Asp385Tyr (c.1153G>T) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about DNAI2 p.Asp385Tyr (c.1153G>T)?

AlphaMissense predicts likely pathogenic (score 0.9243) — an in-silico prediction, not a clinical call.

DNAI2 p.Asp385Tyr

c.1153G>T · VCV3369108

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9243 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9243	likely pathogenic
REVEL	0.699	pathogenic-leaning
SaProt	LLR -15.09	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.2, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 32 kb · p 4.8e-05 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.005% Admixed American · 3/60,006 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000186% 3/1,614,044 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: DNAI2
Protein: p.Asp385Tyr
Coding: c.1153G>T
MANE Select: NM_023036
Type: single nucleotide variant
Location: chr17:74305384 (GRCh38)
Gene constraint: LOEUF 0.966 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 84.27 · 1 PDB

Full DNAI2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAI2 p.Asp385Asn Uncertain significance ★★ ⚠ same residue
DNAI2 p.Asp385= Likely benign ★ same residue
DNAI2 c.1348-1G>A Likely pathogenic ★★ same type
DNAI2 c.1494+1G>A Pathogenic/Likely pathogenic ★★ same type
DNAI2 c.1494+1G>T Pathogenic/Likely pathogenic ★★ same type
DNAI2 c.1495-2A>T Likely pathogenic ★★ same type
DNAI2 c.346-3T>G Pathogenic/Likely pathogenic ★★ same type
DNAI2 c.610+1G>A Pathogenic/Likely pathogenic ★★ 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/dnai2-p-asp385tyr (accessed [today's date]).

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