Is DYNC2H1 p.Ala557Val (c.1670C>T) pathogenic?

DYNC2H1 p.Ala557Val (c.1670C>T) is classified Uncertain significance in DYNC2H1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-15). AlphaMissense: likely benign (0.1674); Very rare (popmax 0.00442%, nfe).

How common is DYNC2H1 p.Ala557Val (c.1670C>T) in the general population?

DYNC2H1 p.Ala557Val (c.1670C>T) is very rare (popmax 0.00442%, nfe) (gnomAD).

What do computational predictors say about DYNC2H1 p.Ala557Val (c.1670C>T)?

AlphaMissense predicts likely benign (score 0.1674) — an in-silico prediction, not a clinical call.

DYNC2H1 p.Ala557Val

c.1670C>T · VCV4913683

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1674 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00442%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.1674	likely benign
REVEL	0.082	moderately 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 5.9	GERP 2, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 61 kb · p 0.56 · regional, not allelic
Overall
CADD	24.1	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 is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00442% European (non-Finnish) · 52/1,177,672 alleles

Filtering AF 0.00343% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0031%

Overall 0.00329% 53/1,610,716 alleles · very rare exomes 48/1,458,656 · genomes 5/152,060 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00442%	22,648
Remaining individualsnot grpmax-eligible	0.0016%	62,360

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.Ala557Val
Coding: c.1670C>T
MANE Select: NM_001377
Type: single nucleotide variant
Location: chr11:103125108 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 557: the 'stem' region

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

Similar variants

DYNC2H1 p.Ala557= Likely benign ★ same residue
DYNC2H1 c.10042+2T>G Pathogenic/Likely pathogenic ★★ same type
DYNC2H1 c.10462-2A>G Likely pathogenic ★★ same type
DYNC2H1 c.10606-14A>G Pathogenic/Likely pathogenic ★★ same type
DYNC2H1 c.10695+1G>A Likely pathogenic ★★ same type
DYNC2H1 c.10813-2A>G Likely pathogenic ★★ same type
DYNC2H1 c.11493+2T>A Likely pathogenic ★★ same type
DYNC2H1 c.11650-1G>A Pathogenic/Likely pathogenic ★★ 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/dync2h1-p-ala557val (accessed [today's date]).

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