Is DYNC2I1 p.Val164Ile (c.490G>A) pathogenic?

DYNC2I1 p.Val164Ile (c.490G>A) is classified Benign in DYNC2I1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.0825); Common (popmax 11%, afr) — too common for a highly-penetrant pathogenic allele; Associated with short-rib thoracic dysplasia 8 with or without polydactyly.

What condition is associated with DYNC2I1 p.Val164Ile (c.490G>A)?

DYNC2I1 p.Val164Ile (c.490G>A) is associated with short-rib thoracic dysplasia 8 with or without polydactyly (ClinVar).

What do computational predictors say about DYNC2I1 p.Val164Ile (c.490G>A)?

AlphaMissense predicts likely benign (score 0.0825) — an in-silico prediction, not a clinical call.

DYNC2I1 p.Val164Ile

Q: How common is DYNC2I1 p.Val164Ile (c.490G>A) in the general population?

DYNC2I1 p.Val164Ile (c.490G>A) is common (popmax 11%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.490G>A · rs78313003 · VCV516235

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0825 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 11%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

short-rib thoracic dysplasia 8 with or without polydactyly

Computational evidence

Protein change
AlphaMissense	0.0825	likely benign
REVEL	0.115	moderately benign-leaning
SaProt	LLR -7.28	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.34	donor loss · deltas
Pangolin	Δ0.53	loss · gain 0.07 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 9.6	GERP 1.1, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 89 kb · p 0.52 · regional, not allelic
Overall
CADD	22.5	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 11% African / African-American · 7,970/72,312 alleles

Filtering AF 10.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 10.7%

Overall 4.72% 72,324/1,531,064 alleles · common exomes 62,853/1,378,782 · genomes 9,471/152,282 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	11%	9
Amishnot grpmax-eligible	8.66%	12
Finnishnot grpmax-eligible	6.13%	16
Remaining individualsnot grpmax-eligible	4.53%	22
European (non-Finnish)	4.43%	23
South Asian	4.39%	23
Ashkenazi Jewishnot grpmax-eligible	4.3%	23
East Asian	3.81%	26
Admixed American	2.84%	35
Middle Eastern	2.1%	48

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: DYNC2I1
Protein: p.Val164Ile
Coding: c.490G>A
MANE Select: NM_018051
dbSNP: rs78313003
Type: single nucleotide variant
Location: chr7:158871562 (GRCh38)
Gene constraint: LOEUF 0.802 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 62.87 · 4 PDB
Residue 164: the 'disordered' region

Full DYNC2I1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

short-rib thoracic dysplasia 8 with or without polydactyly — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DYNC2I1 p.Arg228Ter Pathogenic/Likely pathogenic ★★ same condition
DYNC2I1 p.Arg441Ter Pathogenic/Likely pathogenic ★★ same condition
DYNC2I1 p.Arg642Ter Pathogenic/Likely pathogenic ★★ same condition
DYNC2I1 p.Arg762Ter Pathogenic ★★ same condition
DYNC2I1 p.Ala157Val Uncertain significance ★★ ⚠ same condition
DYNC2I1 p.Ala609Val Uncertain significance ★★ ⚠ same condition
DYNC2I1 p.Ala800Thr Uncertain significance ★★ ⚠ same condition
DYNC2I1 p.Ala822Thr Uncertain significance ★★ ⚠ 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/dync2i1-p-val164ile (accessed [today's date]).

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