Is DNAH9 p.Arg438Ter (c.1312C>T) pathogenic?

DNAH9 p.Arg438Ter (c.1312C>T) is classified Pathogenic in DNAH9 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-07). Ultra-rare (popmax 0.0165%, mid).

How common is DNAH9 p.Arg438Ter (c.1312C>T) in the general population?

DNAH9 p.Arg438Ter (c.1312C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

DNAH9 p.Arg438Ter

c.1312C>T · rs754211366 · VCV2427812

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 6 of 69
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.82	GERP 0.95, phastCons 0.97
Overall
CADD	36.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,060 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000558% 9/1,613,640 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,060
Remaining individualsnot grpmax-eligible	0.0016%	62,496
South Asian	0.0011%	91,066
European (non-Finnish)	0.000509%	196,597

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.Arg438Ter
Coding: c.1312C>T
MANE Select: NM_001372
dbSNP: rs754211366
Type: single nucleotide variant
Location: chr17:11619743 (GRCh38)
Gene constraint: LOEUF 0.775 · pLI <0.01 (gnomAD)
Residue 438: the 'stem' region

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

Similar variants

DNAH9 p.Arg438Gln Likely benign ★★ 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-arg438ter (accessed [today's date]).

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