Is DNAI7 p.Gln604His (c.1812G>C) pathogenic?

DNAI7 p.Gln604His (c.1812G>C) is classified Uncertain significance in DNAI7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-03). AlphaMissense: likely pathogenic (0.7757); Absent from gnomAD v4.1.

How common is DNAI7 p.Gln604His (c.1812G>C) in the general population?

DNAI7 p.Gln604His (c.1812G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DNAI7 p.Gln604His (c.1812G>C)?

AlphaMissense predicts likely pathogenic (score 0.7757) — an in-silico prediction, not a clinical call.

DNAI7 p.Gln604His

c.1812G>C · rs1166400460 · VCV3084341

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7757 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7757	likely pathogenic · top 8% in DNAI7
REVEL	0.282	benign-leaning
SaProt	LLR -5.24	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.023	GERP -4.4, phastCons 0.91
Regional constraint	o/e 0.93	unconstrained · MANE · 87 kb · p 0.044 · regional, not allelic
Overall
CADD	19.59	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM Q598H vs ClinVar Q604H) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DNAI7
Protein: p.Gln604His
Coding: c.1812G>C
MANE Select: NM_018272
dbSNP: rs1166400460
Type: single nucleotide variant
Location: chr12:25110208 (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.Arg348Gln Uncertain significance ★ ⚠ same type
DNAI7 p.Arg39Cys Uncertain significance ★ ⚠ same type
DNAI7 p.Arg54Gln 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-gln604his (accessed [today's date]).

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