Is EMX2 p.Ala5Pro (c.13G>C) pathogenic?

EMX2 p.Ala5Pro (c.13G>C) is classified Uncertain significance in EMX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-06). AlphaMissense: likely benign (0.1111); Ultra-rare (popmax 0.0123%, eas); Associated with Inborn genetic diseases.

What condition is associated with EMX2 p.Ala5Pro (c.13G>C)?

EMX2 p.Ala5Pro (c.13G>C) is associated with Inborn genetic diseases (ClinVar).

How common is EMX2 p.Ala5Pro (c.13G>C) in the general population?

EMX2 p.Ala5Pro (c.13G>C) is ultra-rare (popmax 0.0123%, eas) (gnomAD).

What do computational predictors say about EMX2 p.Ala5Pro (c.13G>C)?

AlphaMissense predicts likely benign (score 0.1111) — an in-silico prediction, not a clinical call.

EMX2 p.Ala5Pro

c.13G>C · VCV3508396

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1111 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0123%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1111	likely benign
REVEL	0.386	indeterminate
SaProt	LLR -6.92	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.8, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 2,389 bp · p 0.33 · regional, not allelic
Overall
CADD	25.3	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

Grpmax group 0.0123% East Asian · 5/40,716 alleles

Filtering AF 0.00481% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0031%

Overall 0.000775% 12/1,548,030 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0123%	8,143
Remaining individualsnot grpmax-eligible	0.01%	9,991
European (non-Finnish)	8.73e-05%	1,145,993

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: EMX2
Protein: p.Ala5Pro
Coding: c.13G>C
MANE Select: NM_004098
Type: single nucleotide variant
Location: chr10:117543280 (GRCh38)
Gene constraint: LOEUF 0.499 · pLI 0.98 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 67.26

Full EMX2 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

EMX2 p.Ala5Gly Uncertain significance ★ ⚠ same residue
EMX2 p.Ala172Asp Uncertain significance ★ ⚠ same condition
EMX2 p.Ala172Thr Uncertain significance ★ ⚠ same condition
EMX2 p.Ala34Val Uncertain significance ★ ⚠ same condition
EMX2 p.Ala95Val Uncertain significance ★ ⚠ same condition
EMX2 p.Arg114Gly Uncertain significance ★ ⚠ same condition
EMX2 p.Asn80Asp Uncertain significance ★ ⚠ same condition
EMX2 p.Asp68Tyr 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/emx2-p-ala5pro (accessed [today's date]).

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