Is DYNLT2B p.Ile97Phe (c.289A>T) pathogenic?

DYNLT2B p.Ile97Phe (c.289A>T) is classified Uncertain significance in DYNLT2B (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-18). AlphaMissense: likely pathogenic (0.5862); Ultra-rare (popmax 0.0312%, nfe).

How common is DYNLT2B p.Ile97Phe (c.289A>T) in the general population?

DYNLT2B p.Ile97Phe (c.289A>T) is ultra-rare (popmax 0.0312%, nfe) (gnomAD).

What do computational predictors say about DYNLT2B p.Ile97Phe (c.289A>T)?

AlphaMissense predicts likely pathogenic (score 0.5862) — an in-silico prediction, not a clinical call.

DYNLT2B p.Ile97Phe

c.289A>T · rs147435808 · VCV2151177

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5862 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0312%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.5862	likely pathogenic
REVEL	0.54	indeterminate
SaProt	LLR -10.75	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 2.6, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 27 kb · p 0.0016 · regional, not allelic
Overall
CADD	27.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0312% European (non-Finnish) · 368/1,179,984 alleles

Filtering AF 0.0285% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0275%

Overall 0.025% 403/1,614,110 alleles · ultra-rare exomes 381/1,461,802 · genomes 22/152,308 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0368%	2,718
European (non-Finnish)grpmax	0.0312%	3,206
Admixed American	0.00833%	12,003
Finnishnot grpmax-eligible	0.00625%	16,008
African / African-American	0.004%	25,017

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: DYNLT2B
Protein: p.Ile97Phe
Coding: c.289A>T
MANE Select: NM_152773
dbSNP: rs147435808
Type: single nucleotide variant
Location: chr3:196306971 (GRCh38)
Gene constraint: LOEUF 1.236 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.89 · 2 PDB
Residue 97: a UniProt-annotated variant site (in srtd17); a β-strand

Full DYNLT2B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DYNLT2B p.Arg88Ter Pathogenic/Likely pathogenic ★★ same type
DYNLT2B p.Arg110His Uncertain significance ★★ same type
DYNLT2B p.Asn119Ser Uncertain significance ★★ ⚠ same type
DYNLT2B p.Gly6Arg Uncertain significance ★★ ⚠ same type
DYNLT2B p.Gly6Val Uncertain significance ★★ ⚠ same type
DYNLT2B p.Ser4Thr Uncertain significance ★★ ⚠ same type
DYNLT2B p.Val95Leu Uncertain significance ★★ ⚠ same type
DYNLT2B c.113+17C>G Benign ★★ 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/dynlt2b-p-ile97phe (accessed [today's date]).

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