Is DYTN p.Pro575Ser (c.1723C>T) pathogenic?

DYTN p.Pro575Ser (c.1723C>T) is classified Uncertain significance in DYTN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-24). AlphaMissense: likely benign (0.1097); Very rare (popmax 0.00891%, eas).

How common is DYTN p.Pro575Ser (c.1723C>T) in the general population?

DYTN p.Pro575Ser (c.1723C>T) is very rare (popmax 0.00891%, eas) (gnomAD).

What do computational predictors say about DYTN p.Pro575Ser (c.1723C>T)?

AlphaMissense predicts likely benign (score 0.1097) — an in-silico prediction, not a clinical call.

DYTN p.Pro575Ser

c.1723C>T · VCV4245983

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1097 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1097	likely benign
REVEL	0.016	strongly benign-leaning
SaProt	LLR -2.46	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 1.3	GERP 1.7, phastCons 0.8
Regional constraint	o/e 1.05	unconstrained · MANE · 66 kb · p 0.15 · regional, not allelic
Overall
CADD	14.17	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 0.00891% East Asian · 4/44,882 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00191%

Overall 0.00294% 43/1,461,260 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,220
Remaining individualsnot grpmax-eligible	0.0064%	15,618
European (non-Finnish)	0.00297%	33,701

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: DYTN
Protein: p.Pro575Ser
Coding: c.1723C>T
MANE Select: NM_001093730
Type: single nucleotide variant
Location: chr2:206651832 (GRCh38)
Gene constraint: LOEUF 1.328 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.89

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

Similar variants

DYTN p.Ala112Thr Uncertain significance ★ ⚠ same type
DYTN p.Ala178Val Uncertain significance ★ ⚠ same type
DYTN p.Ala324Val Uncertain significance ★ ⚠ same type
DYTN p.Ala449Ser Uncertain significance ★ ⚠ same type
DYTN p.Ala465Thr Uncertain significance ★ ⚠ same type
DYTN p.Ala52Pro Uncertain significance ★ ⚠ same type
DYTN p.Ala564Thr Uncertain significance ★ ⚠ same type
DYTN p.Ala567Thr 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/dytn-p-pro575ser (accessed [today's date]).

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