Is BBX p.Ala260Val (c.779C>T) pathogenic?

BBX p.Ala260Val (c.779C>T) is classified Benign in BBX (ClinVar, Single submitter, 1 submitter; last evaluated 2017-06-06). AlphaMissense: likely benign (0.0768); Low-frequency (popmax 1.11%, sas).

How common is BBX p.Ala260Val (c.779C>T) in the general population?

BBX p.Ala260Val (c.779C>T) is low-frequency (popmax 1.11%, sas) (gnomAD).

What do computational predictors say about BBX p.Ala260Val (c.779C>T)?

AlphaMissense predicts likely benign (score 0.0768) — an in-silico prediction, not a clinical call.

BBX p.Ala260Val

c.779C>T · rs150121801 · VCV773704

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0768 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.11%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0768	likely benign
REVEL	0.27	benign-leaning
SaProt	LLR -5.47	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.91	GERP -2.7, phastCons 0.99
Regional constraint	o/e 1.00	unconstrained · MANE · 23 kb · p 0.99 · regional, not allelic
Overall
CADD	9.66	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 1.11% South Asian · 1,014/90,966 alleles

Filtering AF 1.06% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.03%

Overall 0.182% 2,943/1,613,314 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	1.11%	90
Middle Eastern	0.496%	202
Amishnot grpmax-eligible	0.329%	304
Remaining individualsnot grpmax-eligible	0.248%	403
Ashkenazi Jewishnot grpmax-eligible	0.23%	435
European (non-Finnish)	0.134%	744
Admixed American	0.0884%	1,131
Finnishnot grpmax-eligible	0.0406%	2,461
African / African-American	0.0107%	9,375
East Asian	0.00223%	44,802

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: BBX
Protein: p.Ala260Val
Coding: c.779C>T
MANE Select: NM_001142568
dbSNP: rs150121801
Type: single nucleotide variant
Location: chr3:107747993 (GRCh38)
Gene constraint: LOEUF 0.359 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 50.79

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

Similar variants

BBX p.Ala442Thr Benign ★★ same type
BBX p.Ala60= Likely benign ★★ same type
BBX p.Ala892= Benign ★★ same type
BBX p.Ala139Thr Uncertain significance ★ ⚠ same type
BBX p.Ala143Gly Uncertain significance ★ ⚠ same type
BBX p.Ala269Pro Uncertain significance ★ ⚠ same type
BBX p.Ala354Thr Uncertain significance ★ ⚠ same type
BBX p.Ala375Thr 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/bbx-p-ala260val (accessed [today's date]).

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