Is EMX2 p.Ala35= (c.105A>T) pathogenic?

EMX2 p.Ala35= (c.105A>T) is classified Benign/Likely benign in EMX2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-04-01). Rare (popmax 0.902%, amr).

How common is EMX2 p.Ala35= (c.105A>T) in the general population?

EMX2 p.Ala35= (c.105A>T) is rare (popmax 0.902%, amr) (gnomAD).

EMX2 p.Ala35=

c.105A>T · rs373030604 · VCV193271

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.902%, amr)

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 0.24	GERP -4.9, phastCons 0.96
Overall
CADD	10.18	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.902% Admixed American · 487/53,974 alleles

Filtering AF 0.836% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.81%

Overall 0.0426% 670/1,571,416 alleles · rare exomes 564/1,419,614 · genomes 106/151,802 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.902%	111
East Asian	0.16%	625
Remaining individualsnot grpmax-eligible	0.0459%	2,176
African / African-American	0.0448%	2,232
South Asian	0.0139%	7,178
European (non-Finnish)	0.00371%	26,962

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.Ala35=
Coding: c.105A>T
MANE Select: NM_004098
dbSNP: rs373030604
Type: single nucleotide variant
Location: chr10:117543372 (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

Similar variants

EMX2 p.Ser192Thr Uncertain significance ★★ ⚠ same type
EMX2 c.591+6T>C Benign/Likely benign ★★ same type
EMX2 p.Arg156= Benign ★★ same type
EMX2 p.Lys199Gln Likely pathogenic ★ same type
EMX2 p.Val83Leu Pathogenic ★ ⚠ same type
EMX2 p.Ala172Asp Uncertain significance ★ ⚠ same type
EMX2 p.Ala172Thr Uncertain significance ★ ⚠ same type
EMX2 p.Ala34Val 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/emx2-p-ala35 (accessed [today's date]).

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