Is DYNLT2B p.Phe9Ser (c.26T>C) pathogenic?

DYNLT2B p.Phe9Ser (c.26T>C) is classified Uncertain significance in DYNLT2B (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-04). AlphaMissense: likely benign (0.1048); Ultra-rare (popmax 0.0728%, eas).

How common is DYNLT2B p.Phe9Ser (c.26T>C) in the general population?

DYNLT2B p.Phe9Ser (c.26T>C) is ultra-rare (popmax 0.0728%, eas) (gnomAD).

What do computational predictors say about DYNLT2B p.Phe9Ser (c.26T>C)?

AlphaMissense predicts likely benign (score 0.1048) — an in-silico prediction, not a clinical call.

DYNLT2B p.Phe9Ser

c.26T>C · rs200176949 · VCV2416035

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1048 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0728%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1048	likely benign
REVEL	0.092	moderately benign-leaning
SaProt	LLR -2.98	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 1.6	GERP -2.3
Regional constraint	o/e 0.76	unconstrained · MANE · 27 kb · p 0.0016 · regional, not allelic
Overall
CADD	11.57	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 0.0728% East Asian · 28/38,436 alleles

Filtering AF 0.0518% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0446%

Overall 0.00219% 34/1,553,354 alleles · ultra-rare exomes 24/1,401,182 · genomes 10/152,172 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0728%	1,373
Remaining individualsnot grpmax-eligible	0.00498%	20,098
European (non-Finnish)	0.000259%	385,564

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.Phe9Ser
Coding: c.26T>C
MANE Select: NM_152773
dbSNP: rs200176949
Type: single nucleotide variant
Location: chr3:196318127 (GRCh38)
Gene constraint: LOEUF 1.236 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.89 · 2 PDB
Residue 9: 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-phe9ser (accessed [today's date]).

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