Is DYNLT5 p.Pro72Leu (c.215C>T) pathogenic?

DYNLT5 p.Pro72Leu (c.215C>T) is classified Uncertain significance in DYNLT5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-05). AlphaMissense: likely benign (0.2716); Ultra-rare (popmax 0.0155%, sas).

How common is DYNLT5 p.Pro72Leu (c.215C>T) in the general population?

DYNLT5 p.Pro72Leu (c.215C>T) is ultra-rare (popmax 0.0155%, sas) (gnomAD).

What do computational predictors say about DYNLT5 p.Pro72Leu (c.215C>T)?

AlphaMissense predicts likely benign (score 0.2716) — an in-silico prediction, not a clinical call.

DYNLT5 p.Pro72Leu

c.215C>T · VCV3506134

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2716 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0155%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2716	likely benign
REVEL	0.347	indeterminate
SaProt	LLR -13.69	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 23 kb · p 0.34 · regional, not allelic
Overall
CADD	26.7	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 0.0155% South Asian · 14/90,296 alleles

Filtering AF 0.00937% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00751%

Overall 0.000931% 15/1,611,120 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0155%	6,450
Admixed American	0.00168%	59,648

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: DYNLT5
Protein: p.Pro72Leu
Coding: c.215C>T
MANE Select: NM_152665
Type: single nucleotide variant
Location: chr1:66776282 (GRCh38)
Gene constraint: LOEUF 1.657 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.94

Full DYNLT5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DYNLT5 p.Ala169Ser Uncertain significance ★ ⚠ same type
DYNLT5 p.Arg125Gln Uncertain significance ★ ⚠ same type
DYNLT5 p.Arg125Trp Uncertain significance ★ ⚠ same type
DYNLT5 p.Arg37His Uncertain significance ★ ⚠ same type
DYNLT5 p.Arg54Cys Uncertain significance ★ ⚠ same type
DYNLT5 p.Arg54His Uncertain significance ★ ⚠ same type
DYNLT5 p.Asn26His Uncertain significance ★ ⚠ same type
DYNLT5 p.Asn6Lys 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/dynlt5-p-pro72leu (accessed [today's date]).

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