Is DNAH17 p.Pro3228Ser (c.9682C>T) pathogenic?

DNAH17 p.Pro3228Ser (c.9682C>T) is classified Uncertain significance in DNAH17 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-01). AlphaMissense: ambiguous (0.4333); Ultra-rare (popmax 0.0107%, afr); Associated with Inborn genetic diseases.

What condition is associated with DNAH17 p.Pro3228Ser (c.9682C>T)?

DNAH17 p.Pro3228Ser (c.9682C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DNAH17 p.Pro3228Ser (c.9682C>T) in the general population?

DNAH17 p.Pro3228Ser (c.9682C>T) is ultra-rare (popmax 0.0107%, afr) (gnomAD).

What do computational predictors say about DNAH17 p.Pro3228Ser (c.9682C>T)?

AlphaMissense predicts ambiguous (score 0.4333) — an in-silico prediction, not a clinical call.

DNAH17 p.Pro3228Ser

c.9682C>T · VCV4242285

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4333 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0107%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4333	ambiguous
REVEL	0.748	pathogenic-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 151 kb · p 3.8e-12 · regional, not allelic
Overall
CADD	25.0	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 0.0107% African / African-American · 8/75,052 alleles

Filtering AF 0.00527% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.000496% 8/1,613,918 alleles · ultra-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: DNAH17
Protein: p.Pro3228Ser
Coding: c.9682C>T
MANE Select: NM_173628
Type: single nucleotide variant
Location: chr17:78459180 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 (gnomAD)
Residue 3228: a UniProt-annotated variant site (in spgf39); the 'stalk' 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-pro3228ser (accessed [today's date]).

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