Is DNAH9 p.Pro3994= (c.11982A>G) pathogenic?

DNAH9 p.Pro3994= (c.11982A>G) is classified Benign in DNAH9 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-04). Common (popmax 34.4%, mid) — too common for a highly-penetrant pathogenic allele.

DNAH9 p.Pro3994=

Q: How common is DNAH9 p.Pro3994= (c.11982A>G) in the general population?

DNAH9 p.Pro3994= (c.11982A>G) is common (popmax 34.4%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.11982A>G · rs2286303 · VCV402784

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 34.4%, mid) — too common for a highly-penetrant pathogenic allele

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 -11	GERP -4.7
Overall
CADD	0.143	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 34.4% Middle Eastern · 2,083/6,062 alleles

Filtering AF 33.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 32.6%

Overall 30.4% 491,223/1,613,536 alleles · common

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	35.6%	3
Middle Easterngrpmax	34.4%	3
European (non-Finnish)	32.4%	3
Finnishnot grpmax-eligible	31.8%	3
South Asian	31.4%	3
Remaining individualsnot grpmax-eligible	30.2%	3
Amishnot grpmax-eligible	25.7%	4
Admixed American	22%	5
East Asian	16.8%	6
African / African-American	10.3%	10

Ashkenazi Jewish 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: DNAH9
Protein: p.Pro3994=
Coding: c.11982A>G
MANE Select: NM_001372
dbSNP: rs2286303
Type: single nucleotide variant
Location: chr17:11929970 (GRCh38)
Gene constraint: LOEUF 0.775 · pLI <0.01 (gnomAD)
Residue 3994: a UniProt-annotated variant site (in cild40); a UniProt-annotated variant site (in cild40; loss of localization to cilium axonema); the 'aaa 6' region

Full DNAH9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAH9 p.Pro3994Leu Uncertain significance ★ same residue
DNAH9 c.11406+1G>T Likely pathogenic ★★ same type
DNAH9 c.1901+1G>A Likely pathogenic ★★ same type
DNAH9 c.2928+1G>A Likely pathogenic ★★ same type
DNAH9 c.5709+1G>T Likely pathogenic ★★ same type
DNAH9 c.615-2A>G Likely pathogenic ★★ same type
DNAH9 c.6847+1G>A Likely pathogenic ★★ same type
DNAH9 p.Arg1344Ter Pathogenic/Likely pathogenic ★★ 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/dnah9-p-pro3994 (accessed [today's date]).

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