Is DNAH17 p.Arg8Thr (c.23G>C) pathogenic?

DNAH17 p.Arg8Thr (c.23G>C) is classified Uncertain significance in DNAH17 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-03). AlphaMissense: likely pathogenic (0.9234); Very rare (popmax 0.00223%, eas); Associated with Inborn genetic diseases.

What condition is associated with DNAH17 p.Arg8Thr (c.23G>C)?

DNAH17 p.Arg8Thr (c.23G>C) is associated with Inborn genetic diseases (ClinVar).

How common is DNAH17 p.Arg8Thr (c.23G>C) in the general population?

DNAH17 p.Arg8Thr (c.23G>C) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about DNAH17 p.Arg8Thr (c.23G>C)?

AlphaMissense predicts likely pathogenic (score 0.9234) — an in-silico prediction, not a clinical call.

DNAH17 p.Arg8Thr

c.23G>C · VCV4617514

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9234 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

1/2 damaging

AlphaMissense, REVEL

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9234	likely pathogenic
REVEL	0.272	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 7.4	GERP 1.9, phastCons 0.95
Regional constraint	o/e 1.09	unconstrained · MANE · 151 kb · p 3.8e-12 · regional, not allelic
Overall
CADD	22.6	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 0.00223% East Asian · 1/44,880 alleles

Overall 0.000137% 2/1,461,178 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,880
European (non-Finnish)	8.48e-05%	1,179,668

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.Arg8Thr
Coding: c.23G>C
MANE Select: NM_173628
Type: single nucleotide variant
Location: chr17:78575035 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 (gnomAD)
Residue 8: the 'stem' 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-arg8thr (accessed [today's date]).

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