Is DNAH17 p.Ser986= (c.2958C>A) pathogenic?

DNAH17 p.Ser986= (c.2958C>A) is classified Likely benign in DNAH17 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-11-27). Rare (popmax 0.17%, nfe).

How common is DNAH17 p.Ser986= (c.2958C>A) in the general population?

DNAH17 p.Ser986= (c.2958C>A) is rare (popmax 0.17%, nfe) (gnomAD).

DNAH17 p.Ser986=

c.2958C>A · rs61738715 · VCV2578800

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.17%, nfe)

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 -0.11	GERP -2.1, phastCons 0.15
Overall
CADD	2.478	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.17% European (non-Finnish) · 1,991/1,173,280 alleles

Filtering AF 0.163% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.161%

Overall 0.163% 2,609/1,600,998 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.65%	154
Ashkenazi Jewishnot grpmax-eligible	0.247%	405
European (non-Finnish)grpmax	0.17%	589
Remaining individualsnot grpmax-eligible	0.164%	608
Admixed American	0.0292%	3,421
African / African-American	0.0174%	5,757
Middle Eastern	0.0167%	5,976
South Asian	0.00225%	44,426

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser986=
Coding: c.2958C>A
MANE Select: NM_173628
dbSNP: rs61738715
Type: single nucleotide variant
Location: chr17:78532638 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 (gnomAD)
Residue 986: a UniProt-annotated variant site (in spgf39); the 'stem' region

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

Similar variants

DNAH17 c.7752+2T>A Pathogenic/Likely pathogenic ★★ same type
DNAH17 p.Ala1014Val Uncertain significance ★★ ⚠ same type
DNAH17 p.Arg1217Thr Uncertain significance ★★ ⚠ same type
DNAH17 p.Arg2941Gln Uncertain significance ★★ same type
DNAH17 p.Arg4050Gln Uncertain significance ★★ same type
DNAH17 p.Arg4101Gln Uncertain significance ★★ ⚠ same type
DNAH17 p.Arg4246His Uncertain significance ★★ ⚠ same type
DNAH17 p.Arg4303Cys Uncertain significance ★★ same type

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-ser986 (accessed [today's date]).

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