Is DAND5 p.Arg152Cys (c.454C>T) pathogenic?

DAND5 p.Arg152Cys (c.454C>T) is classified Uncertain significance in DAND5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-25). AlphaMissense: likely benign (0.2707); Very rare (popmax 0.00223%, eas).

How common is DAND5 p.Arg152Cys (c.454C>T) in the general population?

DAND5 p.Arg152Cys (c.454C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about DAND5 p.Arg152Cys (c.454C>T)?

AlphaMissense predicts likely benign (score 0.2707) — an in-silico prediction, not a clinical call.

DAND5 p.Arg152Cys

c.454C>T · VCV4237546

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2707 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2707	likely benign
REVEL	0.183	benign-leaning
SaProt	LLR -11.89	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.098	GERP -2.8
Regional constraint	o/e 1.00	unconstrained · MANE · 3,970 bp · p 0.97 · regional, not allelic
Overall
CADD	14.14	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 0.00223% East Asian · 1/44,888 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.00041% 6/1,461,882 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,888
South Asian	0.0011%	91,072
European (non-Finnish)	0.000339%	295,009

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: DAND5
Protein: p.Arg152Cys
Coding: c.454C>T
MANE Select: NM_152654
Type: single nucleotide variant
Location: chr19:12973518 (GRCh38)
Gene constraint: LOEUF 1.521 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.04
Residue 152: the ctck domain; a disulfide bond

Full DAND5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DAND5 p.Arg152Gly Uncertain significance ★ ⚠ same residue
DAND5 p.Ala16Val Uncertain significance ★ ⚠ same type
DAND5 p.Ala62Val Uncertain significance ★ ⚠ same type
DAND5 p.Ala86Ser Uncertain significance ★ ⚠ same type
DAND5 p.Arg112Trp Uncertain significance ★ ⚠ same type
DAND5 p.Arg119Cys Uncertain significance ★ ⚠ same type
DAND5 p.Arg23Thr Uncertain significance ★ ⚠ same type
DAND5 p.Arg30Gln 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/dand5-p-arg152cys (accessed [today's date]).

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