Is EME2 p.Cys79Phe (c.236G>T) pathogenic?

EME2 p.Cys79Phe (c.236G>T) is classified Benign in EME2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-06-10). AlphaMissense: likely benign (0.1426); Rare (popmax 0.756%, afr).

How common is EME2 p.Cys79Phe (c.236G>T) in the general population?

EME2 p.Cys79Phe (c.236G>T) is rare (popmax 0.756%, afr) (gnomAD).

What do computational predictors say about EME2 p.Cys79Phe (c.236G>T)?

AlphaMissense predicts likely benign (score 0.1426) — an in-silico prediction, not a clinical call.

EME2 p.Cys79Phe

c.236G>T · rs190213042 · VCV787432

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1426 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.756%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1426	likely benign
REVEL	0.061	moderately benign-leaning
SaProt	LLR -8.06	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>A here scores Δ0.42 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.16	GERP -1.9, phastCons 0.006
Regional constraint	o/e 1.28	unconstrained · MANE · 3,007 bp · p 4.8e-11 · regional, not allelic
Overall
CADD	13.75	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.756% African / African-American · 557/73,696 alleles

Filtering AF 0.704% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.683%

Overall 0.0431% 680/1,578,974 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.756%	132
Middle Eastern	0.253%	396
Remaining individualsnot grpmax-eligible	0.0618%	1,618
Admixed American	0.0559%	1,790
European (non-Finnish)	0.00316%	31,668
South Asian	0.00113%	88,626

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: EME2
Protein: p.Cys79Phe
Coding: c.236G>T
MANE Select: NM_001257370
dbSNP: rs190213042
Type: single nucleotide variant
Location: chr16:1773463 (GRCh38)
Gene constraint: LOEUF 1.942 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.73 · 1 PDB
Residue 79: a β-strand; the 'nuclease-like domain; forms the post-nick dna binding interface and is involved in dna recognition and bending' region

Full EME2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MRPS34 p.Leu79Arg Uncertain significance ★ ⚠ same residue
MRPS34 p.Leu79= Likely benign ★ same residue
MRPS34 p.Gln32Ter Pathogenic/Likely pathogenic ★★ same type
MRPS34 p.Arg17Pro Uncertain significance ★★ ⚠ same type
MRPS34 p.Arg27Lys Uncertain significance ★★ ⚠ same type
MRPS34 p.Arg63His Uncertain significance ★★ ⚠ same type
MRPS34 p.Arg9Gln Uncertain significance ★★ ⚠ same type
MRPS34 p.Glu39Asp 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/eme2-p-cys79phe (accessed [today's date]).

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