Is DSTN p.Pro164Arg (c.491C>G) pathogenic?

DSTN p.Pro164Arg (c.491C>G) is classified Uncertain significance in DSTN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-04). AlphaMissense: ambiguous (0.4164); Very rare (popmax 0.00669%, eas).

How common is DSTN p.Pro164Arg (c.491C>G) in the general population?

DSTN p.Pro164Arg (c.491C>G) is very rare (popmax 0.00669%, eas) (gnomAD).

What do computational predictors say about DSTN p.Pro164Arg (c.491C>G)?

AlphaMissense predicts ambiguous (score 0.4164) — an in-silico prediction, not a clinical call.

DSTN p.Pro164Arg

c.491C>G · VCV4662287

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4164 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00669%, eas)

Computational evidence

Protein change
AlphaMissense	0.4164	ambiguous
REVEL	0.453	indeterminate
SaProt	LLR -11.30	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 0.75, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 37 kb · p 7.2e-05 · regional, not allelic
Overall
CADD	22.5	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 0.00669% East Asian · 3/44,864 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00108%

Overall 0.00174% 28/1,611,890 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00669%	14,955
Remaining individualsnot grpmax-eligible	0.00321%	31,152
European (non-Finnish)	0.00195%	51,295

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: DSTN
Protein: p.Pro164Arg
Coding: c.491C>G
MANE Select: NM_006870
Type: single nucleotide variant
Location: chr20:17607139 (GRCh38)
Gene constraint: LOEUF 1.005 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.03

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

Similar variants

DSTN p.Ala87Thr Uncertain significance ★ ⚠ same type
DSTN p.Arg81Cys Uncertain significance ★ ⚠ same type
DSTN p.Asp122Gly Uncertain significance ★ ⚠ same type
DSTN p.Glu51Asp Uncertain significance ★ ⚠ same type
DSTN p.Glu51Gly Uncertain significance ★ same type
DSTN p.Gly4Val Uncertain significance ★ ⚠ same type
DSTN p.Ile131Val Uncertain significance ★ ⚠ same type
DSTN p.Ile148Thr 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/dstn-p-pro164arg (accessed [today's date]).

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