Is DYNLT2B p.Ser4Phe (c.11C>T) pathogenic?

DYNLT2B p.Ser4Phe (c.11C>T) is classified Benign/Likely benign in DYNLT2B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-17). AlphaMissense: likely benign (0.1976); Ultra-rare (popmax 0.0273%, nfe).

How common is DYNLT2B p.Ser4Phe (c.11C>T) in the general population?

DYNLT2B p.Ser4Phe (c.11C>T) is ultra-rare (popmax 0.0273%, nfe) (gnomAD).

What do computational predictors say about DYNLT2B p.Ser4Phe (c.11C>T)?

AlphaMissense predicts likely benign (score 0.1976) — an in-silico prediction, not a clinical call.

DYNLT2B p.Ser4Phe

c.11C>T · rs202097551 · VCV2157291

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1976 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0273%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1976	likely benign
REVEL	0.038	moderately benign-leaning
SaProt	LLR -9.92	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 0.62	GERP 0.65
Regional constraint	o/e 0.76	unconstrained · MANE · 27 kb · p 0.0016 · regional, not allelic
Overall
CADD	12.48	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0273% European (non-Finnish) · 314/1,148,392 alleles

Filtering AF 0.0248% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0238%

Overall 0.0556% 854/1,536,102 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.909%	110
Remaining individualsnot grpmax-eligible	0.0689%	1,452
European (non-Finnish)grpmax	0.0273%	3,657
East Asian	0.0265%	3,772
South Asian	0.00482%	20,735
African / African-American	0.00142%	70,318

Finnish 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.Ser4Phe
Coding: c.11C>T
MANE Select: NM_152773
dbSNP: rs202097551
Type: single nucleotide variant
Location: chr3:196318142 (GRCh38)
Gene constraint: LOEUF 1.236 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.89 · 2 PDB
Residue 4: a β-strand

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

Similar variants

DYNLT2B p.Ser4Thr Uncertain significance ★★ ⚠ same residue
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.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-ser4phe (accessed [today's date]).

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