Is DYNLT4 p.Pro85Ser (c.253C>T) pathogenic?

DYNLT4 p.Pro85Ser (c.253C>T) is classified Uncertain significance in DYNLT4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-29). AlphaMissense: likely benign (0.0859); Very rare (popmax 0.00254%, eas).

How common is DYNLT4 p.Pro85Ser (c.253C>T) in the general population?

DYNLT4 p.Pro85Ser (c.253C>T) is very rare (popmax 0.00254%, eas) (gnomAD).

What do computational predictors say about DYNLT4 p.Pro85Ser (c.253C>T)?

AlphaMissense predicts likely benign (score 0.0859) — an in-silico prediction, not a clinical call.

DYNLT4 p.Pro85Ser

c.253C>T · rs1395902843 · VCV2608709

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0859 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00254%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0859	likely benign
REVEL	0.033	moderately benign-leaning
SaProt	LLR -7.04	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.6	GERP 0.59, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 662 bp · p 0.79 · regional, not allelic
Overall
CADD	14.46	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 0.00254% East Asian · 1/39,366 alleles

Overall 0.000198% 3/1,517,412 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00254%	39,366
Remaining individualsnot grpmax-eligible	0.0017%	58,676
European (non-Finnish)	8.78e-05%	1,139,149

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: DYNLT4
Protein: p.Pro85Ser
Coding: c.253C>T
MANE Select: NM_001377534
dbSNP: rs1395902843
Type: single nucleotide variant
Location: chr1:44806416 (GRCh38)
Gene constraint: LOEUF 1.943 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.02
Residue 85: the 'disordered' region

Full DYNLT4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DYNLT4 p.Ala130Ser Uncertain significance ★ ⚠ same type
DYNLT4 p.Ala146Thr Uncertain significance ★ ⚠ same type
DYNLT4 p.Ala146Val Uncertain significance ★ ⚠ same type
DYNLT4 p.Ala195Val Uncertain significance ★ ⚠ same type
DYNLT4 p.Ala41Ser Uncertain significance ★ ⚠ same type
DYNLT4 p.Ala58Thr Uncertain significance ★ ⚠ same type
DYNLT4 p.Ala72Thr Uncertain significance ★ ⚠ same type
DYNLT4 p.Arg102His 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/dynlt4-p-pro85ser (accessed [today's date]).

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