Is DNHD1 p.Arg3542Ter (c.10624C>T) pathogenic?

DNHD1 p.Arg3542Ter (c.10624C>T) is classified Pathogenic in DNHD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-28). Rare (popmax 0.206%, sas).

How common is DNHD1 p.Arg3542Ter (c.10624C>T) in the general population?

DNHD1 p.Arg3542Ter (c.10624C>T) is rare (popmax 0.206%, sas) (gnomAD).

DNHD1 p.Arg3542Ter

c.10624C>T · rs544185938 · VCV1505775

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

rare (popmax 0.206%, sas)

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 32 of 43
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.41	GERP -0.76, phastCons 0.98
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 0.206% South Asian · 173/84,068 alleles

Filtering AF 0.181% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.171%

Overall 0.0153% 238/1,551,718 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.206%	486
Remaining individualsnot grpmax-eligible	0.0116%	8,588
European (non-Finnish)	0.00497%	20,123
African / African-American	0.00137%	73,190

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.Arg3542Ter
Coding: c.10624C>T
MANE Select: NM_144666
dbSNP: rs544185938
Type: single nucleotide variant
Location: chr11:6564672 (GRCh38)
Gene constraint: LOEUF 0.897 · pLI <0.01 (gnomAD)
Residue 3542: 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.Arg2928Ter Pathogenic/Likely pathogenic ★★ same type
DNHD1 p.Arg3978Ter Pathogenic/Likely pathogenic ★★ same type
DNHD1 p.Arg4048Ter Pathogenic/Likely pathogenic ★★ same type
DNHD1 p.Glu1153Ter Pathogenic/Likely pathogenic ★★ same type
DNHD1 p.Tyr2166Ter Pathogenic/Likely pathogenic ★★ same type
DNHD1 p.Arg1582Trp Uncertain significance ★★ same type
DNHD1 p.Arg1873Ser Uncertain significance ★★ ⚠ same type
DNHD1 p.Arg2555Trp Uncertain significance ★★ ⚠ 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-arg3542ter (accessed [today's date]).

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