Is MESP2 p.Pro166Ser (c.496C>T) pathogenic?

MESP2 p.Pro166Ser (c.496C>T) is classified Uncertain significance in MESP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-01). AlphaMissense: likely benign (0.1643); No allele count reported in gnomAD v4.1 (AN 1,461,046).

How common is MESP2 p.Pro166Ser (c.496C>T) in the general population?

MESP2 p.Pro166Ser (c.496C>T) is no allele count reported in gnomAD v4.1 (AN 1,461,046) (gnomAD).

What do computational predictors say about MESP2 p.Pro166Ser (c.496C>T)?

AlphaMissense predicts likely benign (score 0.1643) — an in-silico prediction, not a clinical call.

MESP2 p.Pro166Ser

c.496C>T · rs1968372707 · VCV1026721

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1643 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,461,046)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1643	likely benign
REVEL	0.369	indeterminate
SaProt	LLR -6.68	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.5	GERP 1.2, phastCons 1
Regional constraint	o/e 1.18	unconstrained · MANE · 1,973 bp · p 1.6e-05 · regional, not allelic
Overall
CADD	21.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,461,046). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: MESP2
Protein: p.Pro166Ser
Coding: c.496C>T
MANE Select: NM_001039958
dbSNP: rs1968372707
Type: single nucleotide variant
Location: chr15:89776853 (GRCh38)
Gene constraint: LOEUF 1.656 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.92
Residue 166: the 'disordered' region

Full MESP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MESP2 p.Pro166= Benign/Likely benign ★★ same residue
MESP2 p.Gly77Ter Pathogenic/Likely pathogenic ★★ same type
MESP2 p.Gly81Ter Pathogenic/Likely pathogenic ★★ same type
MESP2 p.Ser39Ter Pathogenic/Likely pathogenic ★★ same type
MESP2 p.Ser42Ter Pathogenic/Likely pathogenic ★★ same type
MESP2 p.Ser4Ter Pathogenic/Likely pathogenic ★★ same type
MESP2 c.*107T>C Uncertain significance ★★ same type
MESP2 p.Ala360Thr 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/mesp2-p-pro166ser (accessed [today's date]).

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