Is DNAI3 p.His676Arg (c.2027A>G) pathogenic?

DNAI3 p.His676Arg (c.2027A>G) is classified Uncertain significance in DNAI3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-12). AlphaMissense: likely benign (0.1522); Ultra-rare (popmax 0.0133%, amr).

How common is DNAI3 p.His676Arg (c.2027A>G) in the general population?

DNAI3 p.His676Arg (c.2027A>G) is ultra-rare (popmax 0.0133%, amr) (gnomAD).

What do computational predictors say about DNAI3 p.His676Arg (c.2027A>G)?

AlphaMissense predicts likely benign (score 0.1522) — an in-silico prediction, not a clinical call.

DNAI3 p.His676Arg

c.2027A>G · rs549526220 · VCV3084267

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1522 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1522	likely benign
REVEL	0.197	benign-leaning
SaProt	LLR -2.08	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 9.1	GERP 1.7, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 28 kb · p 0.23 · regional, not allelic
Overall
CADD	22.3	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 0.0133% Admixed American · 8/60,024 alleles

Filtering AF 0.00661% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00482%

Overall 0.000558% 9/1,614,214 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0133%	7,503
Remaining individualsnot grpmax-eligible	0.0016%	62,508

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.His676Arg
Coding: c.2027A>G
MANE Select: NM_145172
dbSNP: rs549526220
Type: single nucleotide variant
Location: chr1:85124166 (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-his676arg (accessed [today's date]).

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