Is MYCBP2 p.Pro238Ser (c.712C>T) pathogenic?

MYCBP2 p.Pro238Ser (c.712C>T) is classified Uncertain significance in MYCBP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-30). AlphaMissense: likely pathogenic (0.9592); Very rare (popmax 0.0041%, afr); Associated with Inborn genetic diseases.

What condition is associated with MYCBP2 p.Pro238Ser (c.712C>T)?

MYCBP2 p.Pro238Ser (c.712C>T) is associated with Inborn genetic diseases (ClinVar).

How common is MYCBP2 p.Pro238Ser (c.712C>T) in the general population?

MYCBP2 p.Pro238Ser (c.712C>T) is very rare (popmax 0.0041%, afr) (gnomAD).

What do computational predictors say about MYCBP2 p.Pro238Ser (c.712C>T)?

AlphaMissense predicts likely pathogenic (score 0.9592) — an in-silico prediction, not a clinical call.

MYCBP2 p.Pro238Ser

c.712C>T · VCV4114389

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9592 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0041%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9592	likely pathogenic
REVEL	0.373	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 56 kb · p 0.072 · regional, not allelic
Overall
CADD	24.9	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 0.0041% African / African-American · 3/73,160 alleles

Filtering AF 0.00109% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000502%

Overall 0.00197% 3/152,190 alleles · very rare

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: MYCBP2
Protein: p.Pro238Ser
Coding: c.712C>T
MANE Select: NM_015057
Type: single nucleotide variant
Location: chr13:77278794 (GRCh38)
Gene constraint: LOEUF 0.243 · pLI 1.00 (gnomAD)

Full MYCBP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MYCBP2 p.Asp4042Val Uncertain significance ★★ same condition
MYCBP2 p.Asp4087Asn Uncertain significance ★★ same condition
MYCBP2 p.Gly877Ala Uncertain significance ★★ ⚠ same condition
MYCBP2 p.His2087Leu Uncertain significance ★★ ⚠ same condition
MYCBP2 p.Leu3349Phe Uncertain significance ★★ ⚠ same condition
MYCBP2 p.Lys2309Ter Uncertain significance ★★ same condition
MYCBP2 p.Tyr962Cys Uncertain significance ★★ same condition
MYCBP2 p.Ala1038Pro 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/mycbp2-p-pro238ser (accessed [today's date]).

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