Is BEST1 p.Ser71= (c.213C>T) pathogenic?

BEST1 p.Ser71= (c.213C>T) is classified Benign/Likely benign in BEST1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-11-18). Rare (popmax 0.95%, afr); Associated with vitelliform macular dystrophy 2.

What condition is associated with BEST1 p.Ser71= (c.213C>T)?

BEST1 p.Ser71= (c.213C>T) is associated with vitelliform macular dystrophy 2, autosomal dominant vitreoretinochoroidopathy, retinitis pigmentosa (ClinVar).

How common is BEST1 p.Ser71= (c.213C>T) in the general population?

BEST1 p.Ser71= (c.213C>T) is rare (popmax 0.95%, afr) (gnomAD).

How is Best vitelliform macular dystrophy inherited?

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

BEST1 p.Ser71=

c.213C>T · rs57132800 · VCV305119

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.95%, afr)

Conditions

vitelliform macular dystrophy 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.69 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.34	GERP 2.2, phastCons 0.46
Overall
CADD	13.88	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.95% African / African-American · 713/75,066 alleles

Filtering AF 0.892% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.869%

Overall 0.0494% 797/1,614,224 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.95%	105
Admixed American	0.07%	1,429
Remaining individualsnot grpmax-eligible	0.0592%	1,690
Middle Eastern	0.033%	3,031
South Asian	0.0011%	91,090
European (non-Finnish)	0.000169%	590,012

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.Ser71=
Coding: c.213C>T
MANE Select: NM_004183
dbSNP: rs57132800
Type: single nucleotide variant
Location: chr11:61955167 (GRCh38)
Gene constraint: LOEUF 1.28 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.46 · 19 PDB
Residue 71: an α-helix

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

Disease context

vitelliform macular dystrophy 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal dominant vitreoretinochoroidopathy retinitis pigmentosa

For Best vitelliform macular dystrophy (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Childhood
Prevalence: 1-9 / 100 000 (Denmark)

Similar variants

BEST1 p.Ala10Val Pathogenic ★★ same condition
BEST1 p.Ala195Val Pathogenic/Likely pathogenic ★★ ⚠ same condition
BEST1 p.Ala243Val Pathogenic/Likely pathogenic ★★ same condition
BEST1 p.Arg13Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
BEST1 p.Arg141His Pathogenic/Likely pathogenic ★★ ⚠ same condition
BEST1 p.Arg200Ter Pathogenic ★★ same condition
BEST1 p.Arg218Cys Pathogenic/Likely pathogenic ★★ same condition
BEST1 p.Arg218His Pathogenic/Likely pathogenic ★★ ⚠ 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-ser71 (accessed [today's date]).

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