Is MBL2 p.Pro84Ser (c.250C>T) pathogenic?

MBL2 p.Pro84Ser (c.250C>T) is classified Likely benign in MBL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-14). AlphaMissense: likely benign (0.077); Very rare (popmax 0.00253%, sas).

How common is MBL2 p.Pro84Ser (c.250C>T) in the general population?

MBL2 p.Pro84Ser (c.250C>T) is very rare (popmax 0.00253%, sas) (gnomAD).

What do computational predictors say about MBL2 p.Pro84Ser (c.250C>T)?

AlphaMissense predicts likely benign (score 0.077) — an in-silico prediction, not a clinical call.

MBL2 p.Pro84Ser

c.250C>T · VCV4104741

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.077 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00253%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.077	likely benign
REVEL	0.246	benign-leaning
SaProt	LLR -8.78	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 -8.9	GERP -3.9
Regional constraint	o/e 1.04	unconstrained · MANE · 3,495 bp · p 0.49 · regional, not allelic
Overall
CADD	0.002	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 0.00253% South Asian · 2/78,996 alleles

Filtering AF 0.00042% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000157%

Overall 0.000262% 4/1,526,022 alleles · very rare exomes 3/1,373,820 · genomes 1/152,202 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00253%	39,498
European (non-Finnish)	0.000177%	564,675

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: MBL2
Protein: p.Pro84Ser
Coding: c.250C>T
MANE Select: NM_001378373
Type: single nucleotide variant
Location: chr10:52770724 (GRCh38)
Gene constraint: LOEUF 1.5 · pLI 0.03 (gnomAD)
Structure: AlphaFold pLDDT 82.59 · 1 PDB
Residue 84: the collagen-like domain; the 'disordered' region

Full MBL2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MBL2 c.*1135A>G Uncertain significance ★★ same type
MBL2 c.*1711T>G Uncertain significance ★★ same type
MBL2 c.*865A>C Uncertain significance ★★ same type
MBL2 p.Asn136= Uncertain significance ★★ same type
MBL2 p.Asp219Val Uncertain significance ★★ ⚠ same type
MBL2 p.Glu245Lys Uncertain significance ★★ ⚠ same type
MBL2 p.Gly45Ser Uncertain significance ★★ ⚠ same type
MBL2 p.Lys150Thr 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/mbl2-p-pro84ser (accessed [today's date]).

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