Is DNAH17 p.Ser1255= (c.3765C>T) pathogenic?

DNAH17 p.Ser1255= (c.3765C>T) is classified Likely benign in DNAH17 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-07-10). Ultra-rare (popmax 0.0329%, mid); Associated with DNAH17-related disorder.

What condition is associated with DNAH17 p.Ser1255= (c.3765C>T)?

DNAH17 p.Ser1255= (c.3765C>T) is associated with DNAH17-related disorder (ClinVar).

How common is DNAH17 p.Ser1255= (c.3765C>T) in the general population?

DNAH17 p.Ser1255= (c.3765C>T) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

DNAH17 p.Ser1255=

c.3765C>T · rs748132996 · VCV3050731

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Conditions

DNAH17-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -16	GERP -4
Overall
CADD	1.49	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0329% Middle Eastern · 2/6,084 alleles

Filtering AF 0.0058% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00241%

Overall 0.00186% 30/1,613,636 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,042
Finnishnot grpmax-eligible	0.00941%	10,628
Remaining individualsnot grpmax-eligible	0.0064%	15,616
Admixed American	0.005%	20,003
South Asian	0.00329%	30,360
African / African-American	0.00133%	74,938
European (non-Finnish)	0.000932%	107,261

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.Ser1255=
Coding: c.3765C>T
MANE Select: NM_173628
dbSNP: rs748132996
Type: single nucleotide variant
Location: chr17:78525108 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 (gnomAD)
Residue 1255: a UniProt-annotated variant site (in spgf39); the 'stem' region

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

Disease context

DNAH17-related disorder

Similar variants

DNAH17 c.6818+1G>A Likely pathogenic same condition
DNAH17 p.Ala2154Thr Uncertain significance ⚠ same condition
DNAH17 c.10735-5T>G Likely benign same condition
DNAH17 c.11212-7C>T Likely benign same condition
DNAH17 c.11334+4C>T Likely benign same condition
DNAH17 c.11805+5G>A Likely benign same condition
DNAH17 c.12915+7G>T Benign same condition
DNAH17 c.1836-10C>G Likely benign 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-ser1255 (accessed [today's date]).

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