Is DYNC2H1 p.Pro2997Ser (c.8989C>T) pathogenic?

DYNC2H1 p.Pro2997Ser (c.8989C>T) is classified Likely benign in DYNC2H1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-08). AlphaMissense: likely benign (0.1582); Ultra-rare (popmax 0.0287%, sas); Associated with Jeune syndrome.

What condition is associated with DYNC2H1 p.Pro2997Ser (c.8989C>T)?

DYNC2H1 p.Pro2997Ser (c.8989C>T) is associated with Jeune syndrome (ClinVar).

How common is DYNC2H1 p.Pro2997Ser (c.8989C>T) in the general population?

DYNC2H1 p.Pro2997Ser (c.8989C>T) is ultra-rare (popmax 0.0287%, sas) (gnomAD).

What do computational predictors say about DYNC2H1 p.Pro2997Ser (c.8989C>T)?

AlphaMissense predicts likely benign (score 0.1582) — an in-silico prediction, not a clinical call.

DYNC2H1 p.Pro2997Ser

c.8989C>T · rs762604608 · VCV665403

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1582 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0287%, sas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Jeune syndrome

Computational evidence

Protein change
AlphaMissense	0.1582	likely benign
REVEL	0.232	benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 1.8, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 293 kb · p 0.28 · regional, not allelic
Overall
CADD	20.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0287% South Asian · 26/90,716 alleles

Filtering AF 0.0201% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0172%

Overall 0.0018% 29/1,612,168 alleles · ultra-rare exomes 29/1,459,934 · genomes 0/152,234 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0287%	3,489
Admixed American	0.00167%	59,944
Remaining individualsnot grpmax-eligible	0.0016%	62,410
European (non-Finnish)	8.48e-05%	1,178,857

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: DYNC2H1
Protein: p.Pro2997Ser
Coding: c.8989C>T
MANE Select: NM_001377
dbSNP: rs762604608
Type: single nucleotide variant
Location: chr11:103220665 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 2997: the 'stalk' region

Full DYNC2H1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Jeune syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DYNC2H1 p.Pro2997= Likely benign ★ same residue
DYNC2H1 c.10042+2T>G Pathogenic/Likely pathogenic ★★ same condition
DYNC2H1 c.10462-2A>G Likely pathogenic ★★ same condition
DYNC2H1 c.10606-14A>G Pathogenic/Likely pathogenic ★★ same condition
DYNC2H1 c.10695+1G>A Likely pathogenic ★★ same condition
DYNC2H1 c.10813-2A>G Likely pathogenic ★★ same condition
DYNC2H1 c.11493+2T>A Likely pathogenic ★★ same condition
DYNC2H1 c.11650-1G>A Pathogenic/Likely pathogenic ★★ 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/dync2h1-p-pro2997ser (accessed [today's date]).

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