Is BEST1 p.Asp381= (c.1143C>T) pathogenic?

BEST1 p.Asp381= (c.1143C>T) is classified Conflicting classifications of pathogenicity in BEST1 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-12-26). Rare (popmax 0.113%, afr); Associated with retinitis pigmentosa.

What condition is associated with BEST1 p.Asp381= (c.1143C>T)?

BEST1 p.Asp381= (c.1143C>T) is associated with retinitis pigmentosa (ClinVar).

How common is BEST1 p.Asp381= (c.1143C>T) in the general population?

BEST1 p.Asp381= (c.1143C>T) is rare (popmax 0.113%, afr) (gnomAD).

How is Retinitis pigmentosa inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

BEST1 p.Asp381=

c.1143C>T · rs112199774 · VCV305126

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.113%, afr)

Conditions

retinitis pigmentosa

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 -5.8	GERP -3.8
Overall
CADD	0.288	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.113% African / African-American · 85/75,046 alleles

Filtering AF 0.0938% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0866%

Overall 0.0103% 167/1,614,158 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.113%	883
Middle Eastern	0.033%	3,030
Remaining individualsnot grpmax-eligible	0.016%	6,250
Ashkenazi Jewishnot grpmax-eligible	0.0135%	7,402
South Asian	0.0121%	8,280
East Asian	0.00669%	14,958
European (non-Finnish)	0.00424%	23,600
Admixed American	0.00333%	30,008

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: BEST1
Protein: p.Asp381=
Coding: c.1143C>T
MANE Select: NM_004183
dbSNP: rs112199774
Type: single nucleotide variant
Location: chr11:61962297 (GRCh38)
Gene constraint: LOEUF 1.28 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.46 · 19 PDB

Full BEST1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

retinitis pigmentosa — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Retinitis pigmentosa (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

BEST1 p.Asp381Glu Uncertain significance ★★ ⚠ same residue
BEST1 p.Arg255Trp Pathogenic/Likely pathogenic ★★ same condition
BEST1 p.Ala444Thr Uncertain significance ★★ ⚠ same condition
BEST1 p.Arg355Cys Uncertain significance ★★ ⚠ same condition
BEST1 p.Arg355His Uncertain significance ★★ ⚠ same condition
BEST1 p.Arg356Leu Uncertain significance ★★ ⚠ same condition
BEST1 p.Glu423Lys Uncertain significance ★★ ⚠ same condition
BEST1 p.Pro486Leu Uncertain significance ★★ ⚠ same condition

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/best1-p-asp381 (accessed [today's date]).

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