Is MB p.Pro101Thr (c.301C>A) pathogenic?

MB p.Pro101Thr (c.301C>A) is classified Uncertain significance in MB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-15). AlphaMissense: ambiguous (0.417); Absent from gnomAD v4.1.

How common is MB p.Pro101Thr (c.301C>A) in the general population?

MB p.Pro101Thr (c.301C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MB p.Pro101Thr (c.301C>A)?

AlphaMissense predicts ambiguous (score 0.417) — an in-silico prediction, not a clinical call.

MB p.Pro101Thr

c.301C>A · VCV3543725

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.417 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.417	ambiguous
REVEL	0.217	benign-leaning
SaProt	LLR -11.52	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.4	GERP 1.6, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 9,957 bp · p 0.088 · regional, not allelic
Overall
CADD	25.7	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: MB
Protein: p.Pro101Thr
Coding: c.301C>A
MANE Select: NM_005368
Type: single nucleotide variant
Location: chr22:35610901 (GRCh38)
Gene constraint: LOEUF 1.034 · pLI 0.03 (gnomAD)
Structure: AlphaFold pLDDT 97.26 · 1 PDB
Residue 101: the globin domain

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

Similar variants

MB p.His98Tyr Pathogenic/Likely pathogenic ★★ same type
MB p.Leu150Pro Uncertain significance ★★ ⚠ same type
PVALB p.Ala41Val Benign ★★ same type
PVALB p.Gly65Arg Benign ★★ same type
MB p.Ala72Thr Uncertain significance ★ ⚠ same type
MB p.Ala95Val Uncertain significance ★ ⚠ same type
MB p.Arg140Trp Uncertain significance ★ ⚠ same type
MB p.Asp142Gly 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/mb-p-pro101thr (accessed [today's date]).

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