Is COPB1 p.Phe551Val (c.1651T>G) pathogenic?

COPB1 p.Phe551Val (c.1651T>G) is classified Pathogenic in COPB1 (ClinVar, Single submitter, 3 submitters; last evaluated 2024-03-14). AlphaMissense: likely pathogenic (0.9307); Absent from gnomAD v4.1; Associated with Baralle-Macken syndrome.

What condition is associated with COPB1 p.Phe551Val (c.1651T>G)?

COPB1 p.Phe551Val (c.1651T>G) is associated with Baralle-Macken syndrome, microcephaly, cataract (ClinVar).

How common is COPB1 p.Phe551Val (c.1651T>G) in the general population?

COPB1 p.Phe551Val (c.1651T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COPB1 p.Phe551Val (c.1651T>G)?

AlphaMissense predicts likely pathogenic (score 0.9307) — an in-silico prediction, not a clinical call.

COPB1 p.Phe551Val

c.1651T>G · rs1850476947 · VCV996037

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9307 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Baralle-Macken syndrome

Computational evidence

Protein change
AlphaMissense	0.9307	likely pathogenic ✓ concordant with ClinVar
REVEL	0.475	indeterminate
SaProt	LLR -14.37	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.9, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 29 kb · p 8.1e-05 · regional, not allelic
Overall
CADD	28.1	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: COPB1
Protein: p.Phe551Val
Coding: c.1651T>G
MANE Select: NM_001144061
dbSNP: rs1850476947
Type: single nucleotide variant
Location: chr11:14474581 (GRCh38)
Gene constraint: LOEUF 0.269 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 82.55
Residue 551: a UniProt-annotated variant site (in barmacs)

Full COPB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Baralle-Macken syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: microcephaly cataract immunodeficiency disease

Similar variants

COPB1 p.Met16Val Uncertain significance ★★ ⚠ same condition
COPB1 p.Ser410Arg Uncertain significance ★★ ⚠ same condition
COPB1 c.-57-2A>G Conflicting classifications of pathogenicity ★ ⚠ same condition
COPB1 p.Val789Ile Uncertain significance ★ ⚠ same condition
COPB1 c.957+1G>T Pathogenic/Likely pathogenic same condition
COPB1 c.958-4T>G Likely benign ★★ same type
COPB1 p.Leu271= Likely benign ★★ same type
COPB1 c.1455+2T>C 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/copb1-p-phe551val (accessed [today's date]).

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