Is DNAI3 p.Ala290Pro (c.868G>C) pathogenic?

DNAI3 p.Ala290Pro (c.868G>C) is classified Uncertain significance in DNAI3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-13). AlphaMissense: likely pathogenic (0.931); Very rare (popmax 0.00223%, eas).

How common is DNAI3 p.Ala290Pro (c.868G>C) in the general population?

DNAI3 p.Ala290Pro (c.868G>C) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about DNAI3 p.Ala290Pro (c.868G>C)?

AlphaMissense predicts likely pathogenic (score 0.931) — an in-silico prediction, not a clinical call.

DNAI3 p.Ala290Pro

c.868G>C · rs1185249183 · VCV3084285

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.931 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.931	likely pathogenic · top 6% in DNAI3
REVEL	0.433	indeterminate
SaProt	LLR -9.71	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.40 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 27 kb · p 0.45 · regional, not allelic
Overall
CADD	29.0	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 0.00223% East Asian · 1/44,894 alleles

Overall 0.000658% 1/152,046 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: DNAI3
Protein: p.Ala290Pro
Coding: c.868G>C
MANE Select: NM_145172
dbSNP: rs1185249183
Type: single nucleotide variant
Location: chr1:85093468 (GRCh38)
Gene constraint: LOEUF 0.879 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.17 · 1 PDB

Full DNAI3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAI3 c.1350+6C>A Benign ★★ same type
DNAI3 p.Ala308Thr Benign ★★ same type
DNAI3 p.Arg79= Benign ★★ same type
DNAI3 p.Asp577= Benign ★★ same type
DNAI3 p.Glu458= Likely benign ★★ same type
DNAI3 p.Glu751= Benign ★★ same type
DNAI3 p.His788= Benign ★★ same type
DNAI3 p.His817= Benign ★★ 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/dnai3-p-ala290pro (accessed [today's date]).

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