Is MEIS2 p.Pro103Thr (c.307C>A) pathogenic?

MEIS2 p.Pro103Thr (c.307C>A) is classified Uncertain significance in MEIS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-26). AlphaMissense: likely pathogenic (0.9933); Very rare (popmax 8.47e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with MEIS2 p.Pro103Thr (c.307C>A)?

MEIS2 p.Pro103Thr (c.307C>A) is associated with Inborn genetic diseases (ClinVar).

How common is MEIS2 p.Pro103Thr (c.307C>A) in the general population?

MEIS2 p.Pro103Thr (c.307C>A) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about MEIS2 p.Pro103Thr (c.307C>A)?

AlphaMissense predicts likely pathogenic (score 0.9933) — an in-silico prediction, not a clinical call.

MEIS2 p.Pro103Thr

c.307C>A · rs2505255016 · VCV2541211

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9933 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9933	likely pathogenic
REVEL	0.398	indeterminate
SaProt	LLR -13.92	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 1.4, phastCons 1
Regional constraint	o/e 0.52	unconstrained · MANE · 61 kb · p 1.3e-14 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,984 alleles

Overall 6.2e-05% 1/1,614,052 alleles · very rare exomes 1/1,461,758 · genomes 0/152,294 · 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.Pro103Thr
Coding: c.307C>A
MANE Select: NM_170675
dbSNP: rs2505255016
Type: single nucleotide variant
Location: chr15:37096369 (GRCh38)
Gene constraint: LOEUF 0.255 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 63.16 · 4 PDB
Residue 103: the 'required for interaction with pbx1' region

Full MEIS2 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

MEIS2 p.Pro103Leu Uncertain significance ★ ⚠ same residue
MEIS2 p.Asp6Ala Uncertain significance ★★ ⚠ same condition
MEIS2 p.His447Gln Uncertain significance ★★ ⚠ same condition
MEIS2 p.Leu154Ile Uncertain significance ★★ ⚠ same condition
MEIS2 p.Met472Thr Likely benign ★★ same condition
MEIS2 c.640-29G>A Uncertain significance ★ same condition
MEIS2 p.Ala109Ser Uncertain significance ★ ⚠ same condition
MEIS2 p.Ala21Thr 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/meis2-p-pro103thr (accessed [today's date]).

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