Is BEST1 p.Pro341= (c.1023C>T) pathogenic?

BEST1 p.Pro341= (c.1023C>T) is classified Benign/Likely benign in BEST1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-03). Low-frequency (popmax 3.28%, afr); Associated with retinitis pigmentosa.

What condition is associated with BEST1 p.Pro341= (c.1023C>T)?

BEST1 p.Pro341= (c.1023C>T) is associated with retinitis pigmentosa (ClinVar).

How common is BEST1 p.Pro341= (c.1023C>T) in the general population?

BEST1 p.Pro341= (c.1023C>T) is low-frequency (popmax 3.28%, 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.Pro341=

c.1023C>T · rs1801390 · VCV99676

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.28%, afr)

Conditions

retinitis pigmentosa

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.277	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.6	GERP -4.5
Overall
CADD	4.542	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.28% African / African-American · 2,461/74,976 alleles

Filtering AF 3.17% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.13%

Overall 2.43% 39,113/1,611,786 alleles · low-frequency

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	5.46%	18
African / African-Americangrpmax	3.28%	30
European (non-Finnish)	2.54%	39
Remaining individualsnot grpmax-eligible	2.37%	42
Ashkenazi Jewishnot grpmax-eligible	1.57%	64
Admixed American	1.19%	84
Middle Eastern	1.15%	87
South Asian	0.46%	217
Amishnot grpmax-eligible	0.219%	456
East Asian	0.0849%	1,177

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro341=
Coding: c.1023C>T
MANE Select: NM_004183
dbSNP: rs1801390
Type: single nucleotide variant
Location: chr11:61959966 (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.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
BEST1 p.Thr561Ala 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-pro341 (accessed [today's date]).

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