Is EME1 p.Pro151Ser (c.451C>T) pathogenic?

EME1 p.Pro151Ser (c.451C>T) is classified Likely benign in EME1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-20). AlphaMissense: likely benign (0.0687); Very rare (popmax 0.00833%, amr).

How common is EME1 p.Pro151Ser (c.451C>T) in the general population?

EME1 p.Pro151Ser (c.451C>T) is very rare (popmax 0.00833%, amr) (gnomAD).

What do computational predictors say about EME1 p.Pro151Ser (c.451C>T)?

AlphaMissense predicts likely benign (score 0.0687) — an in-silico prediction, not a clinical call.

EME1 p.Pro151Ser

c.451C>T · rs758656129 · VCV2508140

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0687 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00833%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0687	likely benign
REVEL	0.043	moderately benign-leaning
SaProt	LLR -6.13	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.026	GERP -0.82
Regional constraint	o/e 0.93	unconstrained · MANE · 5,727 bp · p 0.068 · regional, not allelic
Overall
CADD	0.195	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 0.00833% Admixed American · 5/60,010 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.000496% 8/1,614,050 alleles · very rare exomes 8/1,461,830 · genomes 0/152,220 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00833%	12,002
Remaining individualsnot grpmax-eligible	0.0032%	31,247
European (non-Finnish)	8.47e-05%	1,180,004

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: EME1
Protein: p.Pro151Ser
Coding: c.451C>T
MANE Select: NM_152463
dbSNP: rs758656129
Type: single nucleotide variant
Location: chr17:50375659 (GRCh38)
Gene constraint: LOEUF 1.248 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.81 · 14 PDB

Full EME1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EME1 p.Ile282Thr Uncertain significance ★★ same type
EME1 p.Lys5Asn Benign ★★ same type
EME1 c.1113-24C>G Uncertain significance ★ same type
EME1 c.1113-33G>T Uncertain significance ★ same type
EME1 c.1113-34A>G Uncertain significance ★ same type
EME1 c.1113-8T>C Uncertain significance ★ same type
EME1 p.Ala235Val Uncertain significance ★ ⚠ same type
EME1 p.Ala24Gly 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/eme1-p-pro151ser (accessed [today's date]).

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