Is DNAI7 p.Arg348Gln (c.1043G>A) pathogenic?

DNAI7 p.Arg348Gln (c.1043G>A) is classified Uncertain significance in DNAI7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-14). AlphaMissense: likely benign (0.0723); Ultra-rare (popmax 0.0522%, afr).

How common is DNAI7 p.Arg348Gln (c.1043G>A) in the general population?

DNAI7 p.Arg348Gln (c.1043G>A) is ultra-rare (popmax 0.0522%, afr) (gnomAD).

What do computational predictors say about DNAI7 p.Arg348Gln (c.1043G>A)?

AlphaMissense predicts likely benign (score 0.0723) — an in-silico prediction, not a clinical call.

DNAI7 p.Arg348Gln

c.1043G>A · VCV3841413

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0723 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0522%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0723	likely benign
REVEL	0.04	moderately benign-leaning
SaProt	LLR -6.41	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.36 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.9	GERP -1.5, phastCons 0.8
Regional constraint	o/e 0.93	unconstrained · MANE · 87 kb · p 0.044 · regional, not allelic
Overall
CADD	8.793	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R342Q vs ClinVar R348Q) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0522% African / African-American · 39/74,742 alleles

Filtering AF 0.0392% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0346%

Overall 0.00417% 67/1,606,698 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0522%	1,916
Remaining individualsnot grpmax-eligible	0.00482%	20,746
South Asian	0.00223%	44,781
European (non-Finnish)	0.00187%	53,509
Finnishnot grpmax-eligible	0.00158%	63,202

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: DNAI7
Protein: p.Arg348Gln
Coding: c.1043G>A
MANE Select: NM_018272
Type: single nucleotide variant
Location: chr12:25123246 (GRCh38)
Gene constraint: LOEUF 1.282 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.01 · 1 PDB

Full DNAI7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAI7 c.300+1G>A Uncertain significance ★ same type
DNAI7 p.Ala570Thr Uncertain significance ★ ⚠ same type
DNAI7 p.Ala65Thr Uncertain significance ★ ⚠ same type
DNAI7 p.Arg235Gly Uncertain significance ★ ⚠ same type
DNAI7 p.Arg311Gly Uncertain significance ★ ⚠ same type
DNAI7 p.Arg39Cys Uncertain significance ★ ⚠ same type
DNAI7 p.Arg54Gln Uncertain significance ★ ⚠ same type
DNAI7 p.Arg62Pro 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/dnai7-p-arg348gln (accessed [today's date]).

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