Is DYNC2H1 p.Phe2765Val (c.8293T>G) pathogenic?

DYNC2H1 p.Phe2765Val (c.8293T>G) is classified Conflicting classifications of pathogenicity in DYNC2H1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-19). AlphaMissense: likely benign (0.1141); Ultra-rare (popmax 0.0582%, nfe); Associated with asphyxiating thoracic dystrophy 3.

What condition is associated with DYNC2H1 p.Phe2765Val (c.8293T>G)?

DYNC2H1 p.Phe2765Val (c.8293T>G) is associated with asphyxiating thoracic dystrophy 3, Jeune syndrome (ClinVar).

How common is DYNC2H1 p.Phe2765Val (c.8293T>G) in the general population?

DYNC2H1 p.Phe2765Val (c.8293T>G) is ultra-rare (popmax 0.0582%, nfe) (gnomAD).

What do computational predictors say about DYNC2H1 p.Phe2765Val (c.8293T>G)?

AlphaMissense predicts likely benign (score 0.1141) — an in-silico prediction, not a clinical call.

DYNC2H1 p.Phe2765Val

c.8293T>G · rs199503535 · VCV302067

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1141 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0582%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

asphyxiating thoracic dystrophy 3

Computational evidence

Protein change
AlphaMissense	0.1141	likely benign
REVEL	0.197	benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5.1	GERP 1.3, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 293 kb · p 0.28 · regional, not allelic
Overall
CADD	22.2	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 0.0582% European (non-Finnish) · 684/1,175,928 alleles

Filtering AF 0.0545% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0531%

Overall 0.045% 723/1,607,014 alleles · ultra-rare exomes 674/1,454,716 · genomes 49/152,298 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0582%	1,719
Remaining individualsnot grpmax-eligible	0.0241%	4,148
South Asian	0.02%	5,010
African / African-American	0.00401%	24,933
Admixed American	0.00336%	29,767
Finnishnot grpmax-eligible	0.00158%	63,284

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.Phe2765Val
Coding: c.8293T>G
MANE Select: NM_001377
dbSNP: rs199503535
Type: single nucleotide variant
Location: chr11:103203758 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 2765: an α-helix; the 'aaa 4' region

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

Disease context

asphyxiating thoracic dystrophy 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Jeune syndrome

Similar variants

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
DYNC2H1 c.12156+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-phe2765val (accessed [today's date]).

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