Is DNAI3 p.Arg828Ser (c.2482C>A) pathogenic?

DNAI3 p.Arg828Ser (c.2482C>A) is classified Uncertain significance in DNAI3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-28). AlphaMissense: likely pathogenic (0.9137); Very rare (popmax 0.000932%, nfe).

How common is DNAI3 p.Arg828Ser (c.2482C>A) in the general population?

DNAI3 p.Arg828Ser (c.2482C>A) is very rare (popmax 0.000932%, nfe) (gnomAD).

What do computational predictors say about DNAI3 p.Arg828Ser (c.2482C>A)?

AlphaMissense predicts likely pathogenic (score 0.9137) — an in-silico prediction, not a clinical call.

DNAI3 p.Arg828Ser

c.2482C>A · VCV3841387

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9137 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000932%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9137	likely pathogenic · top 7% in DNAI3
REVEL	0.231	benign-leaning
SaProt	LLR -11.71	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.77 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4	GERP 1.4, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 28 kb · p 0.23 · regional, not allelic
Overall
CADD	22.6	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 0.000932% European (non-Finnish) · 11/1,179,788 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000682% 11/1,613,412 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.Arg828Ser
Coding: c.2482C>A
MANE Select: NM_145172
Type: single nucleotide variant
Location: chr1:85130062 (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 p.Arg828Cys Uncertain significance ★ same residue
DNAI3 p.Arg828His Uncertain significance ★ ⚠ same residue
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

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-arg828ser (accessed [today's date]).

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