Is DYNC2I2 p.Pro155Leu (c.464C>T) pathogenic?

DYNC2I2 p.Pro155Leu (c.464C>T) is classified Uncertain significance in DYNC2I2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-04). AlphaMissense: likely benign (0.0922); Very rare (popmax 0.00878%, sas).

How common is DYNC2I2 p.Pro155Leu (c.464C>T) in the general population?

DYNC2I2 p.Pro155Leu (c.464C>T) is very rare (popmax 0.00878%, sas) (gnomAD).

What do computational predictors say about DYNC2I2 p.Pro155Leu (c.464C>T)?

AlphaMissense predicts likely benign (score 0.0922) — an in-silico prediction, not a clinical call.

DYNC2I2 p.Pro155Leu

c.464C>T · rs775372053 · VCV2428803

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0922 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00878%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0922	likely benign
REVEL	0.352	indeterminate
SaProt	LLR -7.95	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.5, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 23 kb · p 0.59 · regional, not allelic
Overall
CADD	25.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00878% South Asian · 8/91,072 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00312%

Overall 0.00143% 23/1,613,182 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00878%	11,384
Remaining individualsnot grpmax-eligible	0.0048%	20,823
African / African-American	0.004%	24,975
European (non-Finnish)	0.000763%	131,105

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: DYNC2I2
Protein: p.Pro155Leu
Coding: c.464C>T
MANE Select: NM_052844
dbSNP: rs775372053
Type: single nucleotide variant
Location: chr9:128636999 (GRCh38)
Gene constraint: LOEUF 1.036 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.66 · 4 PDB

Full DYNC2I2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DYNC2I2 p.Pro155= Likely benign ★ same residue
DYNC2I2 c.1372+1G>A Pathogenic/Likely pathogenic ★★ same type
DYNC2I2 p.Arg121Ter Pathogenic ★★ same type
DYNC2I2 p.Arg182Trp Pathogenic/Likely pathogenic ★★ ⚠ same type
DYNC2I2 p.Arg447Trp Pathogenic/Likely pathogenic ★★ same type
DYNC2I2 p.Ala131Val Uncertain significance ★★ ⚠ same type
DYNC2I2 p.Ala13Gly Uncertain significance ★★ ⚠ same type
DYNC2I2 p.Ala219Thr 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/dync2i2-p-pro155leu (accessed [today's date]).

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