Is RARA p.Asp433= (c.1299C>T) pathogenic?

RARA p.Asp433= (c.1299C>T) is classified Likely benign in RARA (ClinVar, Single submitter, 1 submitter; last evaluated 2018-05-21). Ultra-rare (popmax 0.0739%, amr).

How common is RARA p.Asp433= (c.1299C>T) in the general population?

RARA p.Asp433= (c.1299C>T) is ultra-rare (popmax 0.0739%, amr) (gnomAD).

RARA p.Asp433=

c.1299C>T · rs762021232 · VCV745170

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0739%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -11	GERP -3
Overall
CADD	0.194	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0739% Admixed American · 35/47,372 alleles

Filtering AF 0.0545% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0479%

Overall 0.00458% 68/1,486,016 alleles · ultra-rare exomes 44/1,362,494 · genomes 24/123,522 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0739%	1,353
South Asian	0.0108%	9,234
Remaining individualsnot grpmax-eligible	0.00868%	11,516
African / African-American	0.00632%	15,821
East Asian	0.00251%	39,796
Finnishnot grpmax-eligible	0.00186%	53,720
European (non-Finnish)	0.00117%	85,214

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: RARA
Protein: p.Asp433=
Coding: c.1299C>T
MANE Select: NM_000964
dbSNP: rs762021232
Type: single nucleotide variant
Location: chr17:40356136 (GRCh38)
Gene constraint: LOEUF 0.254 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.49 · 14 PDB
Residue 433: the 'disordered' region

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

Similar variants

RARA p.Pro279= Benign ★★ same type
RARA p.Ala104Thr Uncertain significance ★ ⚠ same type
RARA p.Ala438Val Uncertain significance ★ ⚠ same type
RARA p.Arg162Gln Uncertain significance ★ ⚠ same type
RARA p.Arg276Gln Conflicting classifications of pathogenicity ★ ⚠ same type
RARA p.Arg276Trp Uncertain significance ★ ⚠ same type
RARA p.Arg347Leu Uncertain significance ★ ⚠ same type
RARA p.Arg370Cys 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/rara-p-asp433 (accessed [today's date]).

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