Is DNAH17 p.Arg4285Trp (c.12853C>T) pathogenic?

DNAH17 p.Arg4285Trp (c.12853C>T) is classified Uncertain significance in DNAH17 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-08). AlphaMissense: likely benign (0.2705); Very rare (popmax 0.00879%, sas); Associated with Inborn genetic diseases.

What condition is associated with DNAH17 p.Arg4285Trp (c.12853C>T)?

DNAH17 p.Arg4285Trp (c.12853C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DNAH17 p.Arg4285Trp (c.12853C>T) in the general population?

DNAH17 p.Arg4285Trp (c.12853C>T) is very rare (popmax 0.00879%, sas) (gnomAD).

What do computational predictors say about DNAH17 p.Arg4285Trp (c.12853C>T)?

AlphaMissense predicts likely benign (score 0.2705) — an in-silico prediction, not a clinical call.

DNAH17 p.Arg4285Trp

c.12853C>T · rs376002860 · VCV2598838

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2705 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00879%, sas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2705	likely benign
REVEL	0.239	benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.6	GERP -0.66, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 151 kb · p 3.8e-12 · regional, not allelic
Overall
CADD	23.7	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00879% South Asian · 8/91,004 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00312%

Overall 0.00372% 60/1,613,690 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00879%	11,376
European (non-Finnish)	0.00398%	25,101
East Asian	0.00223%	44,868
Admixed American	0.00167%	59,994
Remaining individualsnot grpmax-eligible	0.0016%	62,480
Finnishnot grpmax-eligible	0.00156%	63,998
African / African-American	0.00133%	75,040

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.Arg4285Trp
Coding: c.12853C>T
MANE Select: NM_173628
dbSNP: rs376002860
Type: single nucleotide variant
Location: chr17:78426519 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 (gnomAD)
Residue 4285: a UniProt-annotated variant site (in spgf39)

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.Arg4285Gln Likely benign ★★ same residue
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

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-arg4285trp (accessed [today's date]).

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