Is DNHD1 p.Leu4481fs (c.13441_13447del) pathogenic?

DNHD1 p.Leu4481fs (c.1344113447del) is classified Pathogenic in DNHD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-28). Ultra-rare (popmax 0.038%, eas).

How common is DNHD1 p.Leu4481fs (c.13441_13447del) in the general population?

DNHD1 p.Leu4481fs (c.13441_13447del) is ultra-rare (popmax 0.038%, eas) (gnomAD).

DNHD1 p.Leu4481fs

c.13441_13447del · rs368113841 · VCV2197413

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.038%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 42 of 43
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.2	GERP -3.2
Overall
CADD	35.0	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 0.038% East Asian · 17/44,698 alleles

Filtering AF 0.0242% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0198%

Overall 0.00106% 17/1,607,958 alleles · ultra-rare

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: DNHD1
Protein: p.Leu4481fs
Coding: c.13441_13447del
MANE Select: NM_144666
dbSNP: rs368113841
Type: Deletion
Location: chr11:6570953 (GRCh38)
Gene constraint: LOEUF 0.897 · pLI <0.01 (gnomAD)
Residue 4481: a UniProt-annotated variant site (in spgf65); a UniProt-annotated variant site (in spgf65; low expression, if any, in sperm flagella)

Full DNHD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNHD1 p.Ala3219fs Likely pathogenic ★ same type
DNHD1 p.Ala4403fs Pathogenic ★ same type
DNHD1 p.Cys2065fs Pathogenic ★ same type
DNHD1 p.Gln754fs Pathogenic ★ same type
DNHD1 p.Glu4334fs Likely pathogenic ★ same type
DNHD1 p.Gly768fs Pathogenic ★ same type
DNHD1 p.His1175fs Pathogenic ★ same type
DNHD1 p.Ile3016fs 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/dnhd1-p-leu4481fs (accessed [today's date]).

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