Is DNHD1 p.Leu2987Pro (c.8960T>C) pathogenic?

DNHD1 p.Leu2987Pro (c.8960T>C) is classified Benign in DNHD1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2019-12-31). AlphaMissense: likely benign (0.0651); Low-frequency (popmax 1.62%, afr).

How common is DNHD1 p.Leu2987Pro (c.8960T>C) in the general population?

DNHD1 p.Leu2987Pro (c.8960T>C) is low-frequency (popmax 1.62%, afr) (gnomAD).

What do computational predictors say about DNHD1 p.Leu2987Pro (c.8960T>C)?

AlphaMissense predicts likely benign (score 0.0651) — an in-silico prediction, not a clinical call.

DNHD1 p.Leu2987Pro

c.8960T>C · rs116082386 · VCV724237

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0651 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.62%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.0651	likely benign
REVEL	0.045	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.1	GERP -3.1
Regional constraint	o/e 0.90	unconstrained · MANE · 66 kb · p 5.3e-11 · regional, not allelic
Overall
CADD	3.209	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.62% African / African-American · 1,182/73,130 alleles

Filtering AF 1.54% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.51%

Overall 0.088% 1,365/1,551,568 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.62%	62
Admixed American	0.147%	680
Remaining individualsnot grpmax-eligible	0.13%	771
Middle Eastern	0.0168%	5,968
East Asian	0.00489%	20,453
South Asian	0.00476%	21,013
European (non-Finnish)	0.00201%	49,868

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.Leu2987Pro
Coding: c.8960T>C
MANE Select: NM_144666
dbSNP: rs116082386
Type: single nucleotide variant
Location: chr11:6558255 (GRCh38)
Gene constraint: LOEUF 0.897 · pLI <0.01 (gnomAD)
Residue 2987: 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-leu2987pro (accessed [today's date]).

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