Is MEIS2 p.Pro32= (c.96G>T) pathogenic?

MEIS2 p.Pro32= (c.96G>T) is classified Likely benign in MEIS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-11). Very rare (popmax 0.00134%, afr); Associated with cardiac malformation, cleft lip/palate, microcephaly, and digital anomalies.

What condition is associated with MEIS2 p.Pro32= (c.96G>T)?

MEIS2 p.Pro32= (c.96G>T) is associated with cardiac malformation, cleft lip/palate, microcephaly, and digital anomalies (ClinVar).

How common is MEIS2 p.Pro32= (c.96G>T) in the general population?

MEIS2 p.Pro32= (c.96G>T) is very rare (popmax 0.00134%, afr) (gnomAD).

MEIS2 p.Pro32=

c.96G>T · rs1301048671 · VCV532740

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Conditions

cardiac malformation, cleft lip/palate, microcephaly, and digital anomalies

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.81	GERP -2.2, phastCons 1
Overall
CADD	14.5	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,802 alleles

Overall 6.2e-05% 1/1,613,240 alleles · very rare exomes 0/1,461,348 · genomes 1/151,892 · joint denominator

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: MEIS2
Protein: p.Pro32=
Coding: c.96G>T
MANE Select: NM_170675
dbSNP: rs1301048671
Type: single nucleotide variant
Location: chr15:37098116 (GRCh38)
Gene constraint: LOEUF 0.255 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 63.16 · 4 PDB

Full MEIS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cardiac malformation, cleft lip/palate, microcephaly, and digital anomalies — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MEIS2 p.Arg174Ter Pathogenic ★★ same condition
MEIS2 p.Arg219Ter Pathogenic/Likely pathogenic ★★ same condition
MEIS2 p.Asp169Asn Uncertain significance ★★ ⚠ same condition
MEIS2 p.Asp6Ala Uncertain significance ★★ ⚠ same condition
MEIS2 p.Ile33Val Uncertain significance ★★ ⚠ same condition
MEIS2 p.Pro416Arg Uncertain significance ★★ ⚠ same condition
MEIS2 c.13-19C>A Benign/Likely benign ★★ same condition
MEIS2 c.754+7G>C Likely benign ★★ 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/meis2-p-pro32 (accessed [today's date]).

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