Is DNHD1 p.Pro4577Ser (c.13729C>T) pathogenic?

DNHD1 p.Pro4577Ser (c.13729C>T) is classified Likely benign in DNHD1 (ClinVar, Single submitter, 2 submitters; last evaluated 2019-12-31). AlphaMissense: likely benign (0.1072); Rare (popmax 0.663%, sas).

How common is DNHD1 p.Pro4577Ser (c.13729C>T) in the general population?

DNHD1 p.Pro4577Ser (c.13729C>T) is rare (popmax 0.663%, sas) (gnomAD).

What do computational predictors say about DNHD1 p.Pro4577Ser (c.13729C>T)?

AlphaMissense predicts likely benign (score 0.1072) — an in-silico prediction, not a clinical call.

DNHD1 p.Pro4577Ser

c.13729C>T · rs139951286 · VCV721008

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1072 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.663%, sas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.1072	likely benign
REVEL	0.022	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 0.26	GERP -2, phastCons 0.004
Regional constraint	o/e 1.05	unconstrained · MANE · 3,234 bp · p 0.2 · regional, not allelic
Overall
CADD	5.646	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 0.663% South Asian · 603/90,950 alleles

Filtering AF 0.619% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.602%

Overall 0.247% 3,978/1,612,598 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.663%	151
Remaining individualsnot grpmax-eligible	0.341%	293
Middle Eastern	0.264%	379
European (non-Finnish)	0.248%	403
Admixed American	0.239%	419
Ashkenazi Jewishnot grpmax-eligible	0.0812%	1,232
African / African-American	0.0533%	1,876
Finnishnot grpmax-eligible	0.019%	5,260
East Asian	0.00223%	44,836

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.Pro4577Ser
Coding: c.13729C>T
MANE Select: NM_144666
dbSNP: rs139951286
Type: single nucleotide variant
Location: chr11:6571241 (GRCh38)
Gene constraint: LOEUF 0.897 · pLI <0.01 (gnomAD)
Residue 4577: 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

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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-pro4577ser (accessed [today's date]).

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