Is DNHD1 p.Arg1913fs (c.5737_5738insAT) pathogenic?

DNHD1 p.Arg1913fs (c.57375738insAT) is classified Likely benign in DNHD1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-03-28). Low-frequency (popmax 1.07%, afr); Associated with DNHD1-related disorder.

What condition is associated with DNHD1 p.Arg1913fs (c.5737_5738insAT)?

DNHD1 p.Arg1913fs (c.5737_5738insAT) is associated with DNHD1-related disorder (ClinVar).

How common is DNHD1 p.Arg1913fs (c.5737_5738insAT) in the general population?

DNHD1 p.Arg1913fs (c.5737_5738insAT) is low-frequency (popmax 1.07%, afr) (gnomAD).

DNHD1 p.Arg1913fs

c.5737_5738insAT · rs1554888382 · VCV3051131

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

low-frequency (popmax 1.07%, afr)

Conditions

DNHD1-related disorder

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 21 of 43
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.8	GERP 1.6, phastCons 0.86
Overall
CADD	24.8	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 1.07% African / African-American · 780/73,152 alleles

Filtering AF 1% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.979%

Overall 0.0672% 1,043/1,551,728 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.07%	94
Admixed American	0.1%	1,000
Remaining individualsnot grpmax-eligible	0.0699%	1,432
Middle Eastern	0.0501%	1,997
East Asian	0.0244%	4,091
European (non-Finnish)	0.0133%	7,497
South Asian	0.00476%	21,013

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.Arg1913fs
Coding: c.5737_5738insAT
MANE Select: NM_144666
dbSNP: rs1554888382
Type: Insertion
Location: chr11:6546676 (GRCh38)
Gene constraint: LOEUF 0.897 · pLI <0.01 (gnomAD)
Residue 1913: a UniProt-annotated variant site (in spgf65)

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

Disease context

DNHD1-related disorder

Similar variants

DNHD1 p.Arg1913His Uncertain significance ★ ⚠ same residue
DNHD1 p.Glu4486Lys Uncertain significance ★★ ⚠ same condition
DNHD1 p.His4162Leu Uncertain significance ★★ ⚠ same condition
DNHD1 p.Arg2840Gln Uncertain significance ★ ⚠ same condition
DNHD1 p.Gln895Ter Conflicting classifications of pathogenicity ★ same condition
DNHD1 p.His3335Arg Uncertain significance ★ ⚠ same condition
DNHD1 p.Ala657Ser Uncertain significance ⚠ same condition
DNHD1 p.Glu971Lys Uncertain significance ⚠ 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/dnhd1-p-arg1913fs (accessed [today's date]).

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