Is DYNC2H1 p.Gln676Pro (c.2027A>C) pathogenic?

DYNC2H1 p.Gln676Pro (c.2027A>C) is classified Uncertain significance in DYNC2H1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-05). AlphaMissense: ambiguous (0.5636); Very rare (popmax 0.00401%, afr); Associated with Inborn genetic diseases.

What condition is associated with DYNC2H1 p.Gln676Pro (c.2027A>C)?

DYNC2H1 p.Gln676Pro (c.2027A>C) is associated with Inborn genetic diseases, Jeune syndrome (ClinVar).

How common is DYNC2H1 p.Gln676Pro (c.2027A>C) in the general population?

DYNC2H1 p.Gln676Pro (c.2027A>C) is very rare (popmax 0.00401%, afr) (gnomAD).

What do computational predictors say about DYNC2H1 p.Gln676Pro (c.2027A>C)?

AlphaMissense predicts ambiguous (score 0.5636) — an in-silico prediction, not a clinical call.

DYNC2H1 p.Gln676Pro

c.2027A>C · rs752041287 · VCV1429612

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5636 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5636	ambiguous
REVEL	0.194	benign-leaning
SaProt	—	not scored · why
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 9.2	GERP 2.4, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 61 kb · p 0.56 · regional, not allelic
Overall
CADD	21.1	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 0.00401% African / African-American · 3/74,884 alleles

Filtering AF 0.00122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00161% 26/1,612,812 alleles · very rare exomes 21/1,460,620 · genomes 5/152,192 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,961
European (non-Finnish)	0.00187%	53,617
Remaining individualsnot grpmax-eligible	0.0016%	62,418

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.Gln676Pro
Coding: c.2027A>C
MANE Select: NM_001377
dbSNP: rs752041287
Type: single nucleotide variant
Location: chr11:103133628 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 676: the 'stem' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Jeune syndrome

Similar variants

DYNC2H1 p.Gln676Ter Likely pathogenic ★ 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-gln676pro (accessed [today's date]).

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