Is DNAH5 p.Arg2255Ter (c.6763C>T) pathogenic?

DNAH5 p.Arg2255Ter (c.6763C>T) is classified Pathogenic/Likely pathogenic in DNAH5 (ClinVar, Multiple submitters, 14 submitters; last evaluated 2025-09-24). Very rare (popmax 0.00401%, afr); Associated with DNAH5-related disorders.

What condition is associated with DNAH5 p.Arg2255Ter (c.6763C>T)?

DNAH5 p.Arg2255Ter (c.6763C>T) is associated with DNAH5-related disorders, infertility disorder, primary ciliary dyskinesia 3 (ClinVar).

How common is DNAH5 p.Arg2255Ter (c.6763C>T) in the general population?

DNAH5 p.Arg2255Ter (c.6763C>T) is very rare (popmax 0.00401%, afr) (gnomAD).

DNAH5 p.Arg2255Ter

c.6763C>T · rs745918507 · VCV454795

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 14 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Conditions

DNAH5-related disorders

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 41 of 79
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	GERP -3.1, phastCons 1
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 0.00401% African / African-American · 3/74,860 alleles

Filtering AF 0.00157% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00134%

Overall 0.00205% 33/1,613,686 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,953
Remaining individualsnot grpmax-eligible	0.0032%	31,239
European (non-Finnish)	0.00229%	43,703
South Asian	0.0011%	91,074

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: DNAH5
Protein: p.Arg2255Ter
Coding: c.6763C>T
MANE Select: NM_001369
dbSNP: rs745918507
Type: single nucleotide variant
Location: chr5:13820424 (GRCh38)
Gene constraint: LOEUF 0.764 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 2255: the 'aaa 2' region

Full DNAH5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

DNAH5-related disorders

Also linked: infertility disorder primary ciliary dyskinesia 3 primary ciliary dyskinesia

Similar variants

DNAH5 p.Arg2255Gln Uncertain significance ★ same residue
DNAH5 p.Arg2255= Likely benign ★ same residue
DNAH5 c.10555+1G>C Likely pathogenic ★★ same condition
DNAH5 c.1089+1G>A Pathogenic ★★ same condition
DNAH5 c.11028+2T>C Pathogenic/Likely pathogenic ★★ same condition
DNAH5 c.11029-2A>T Pathogenic/Likely pathogenic ★★ same condition
DNAH5 c.11571-1G>A Pathogenic ★★ same condition
DNAH5 c.12910-1G>C Pathogenic/Likely pathogenic ★★ 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/dnah5-p-arg2255ter (accessed [today's date]).

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