Is DNAH17 p.Ala2289Pro (c.6865G>C) pathogenic?

DNAH17 p.Ala2289Pro (c.6865G>C) is classified Uncertain significance in DNAH17 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-30). AlphaMissense: likely pathogenic (0.787); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with DNAH17 p.Ala2289Pro (c.6865G>C)?

DNAH17 p.Ala2289Pro (c.6865G>C) is associated with Inborn genetic diseases (ClinVar).

How common is DNAH17 p.Ala2289Pro (c.6865G>C) in the general population?

DNAH17 p.Ala2289Pro (c.6865G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DNAH17 p.Ala2289Pro (c.6865G>C)?

AlphaMissense predicts likely pathogenic (score 0.787) — an in-silico prediction, not a clinical call.

DNAH17 p.Ala2289Pro

c.6865G>C · VCV4617554

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.787 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, REVEL

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.787	likely pathogenic
REVEL	0.278	benign-leaning
⇒ AlphaMissense calls this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2.2, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 151 kb · p 3.8e-12 · regional, not allelic
Overall
CADD	24.5	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

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: DNAH17
Protein: p.Ala2289Pro
Coding: c.6865G>C
MANE Select: NM_173628
Type: single nucleotide variant
Location: chr17:78486460 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 (gnomAD)
Residue 2289: a UniProt-annotated variant site (in spgf39); the 'aaa 2' region

Full DNAH17 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DNAH17 p.Ala1014Val Uncertain significance ★★ ⚠ same condition
DNAH17 p.Arg1217Thr Uncertain significance ★★ ⚠ same condition
DNAH17 p.Arg2941Gln Uncertain significance ★★ same condition
DNAH17 p.Arg4050Gln Uncertain significance ★★ same condition
DNAH17 p.Arg4101Gln Uncertain significance ★★ ⚠ same condition
DNAH17 p.Arg4246His Uncertain significance ★★ ⚠ same condition
DNAH17 p.Arg4303Cys Uncertain significance ★★ same condition
DNAH17 p.Asn1230Thr Uncertain significance ★★ ⚠ same condition

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/dnah17-p-ala2289pro (accessed [today's date]).

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