Is EML1 p.Ser115= (c.345C>T) pathogenic?

EML1 p.Ser115= (c.345C>T) is classified Benign/Likely benign in EML1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-13). Rare (popmax 0.42%, afr).

How common is EML1 p.Ser115= (c.345C>T) in the general population?

EML1 p.Ser115= (c.345C>T) is rare (popmax 0.42%, afr) (gnomAD).

EML1 p.Ser115=

c.345C>T · rs139395720 · VCV744091

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.42%, afr)

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 -10	GERP -3.1
Overall
CADD	0.168	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.42% African / African-American · 315/75,044 alleles

Filtering AF 0.382% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.367%

Overall 0.0273% 441/1,614,160 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.42%	238
Remaining individualsnot grpmax-eligible	0.0384%	2,604
Admixed American	0.0233%	4,288
European (non-Finnish)	0.0072%	13,883
South Asian	0.00329%	30,361

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: EML1
Protein: p.Ser115=
Coding: c.345C>T
MANE Select: NM_004434
dbSNP: rs139395720
Type: single nucleotide variant
Location: chr14:99865608 (GRCh38)
Gene constraint: LOEUF 0.36 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 86.49 · 1 PDB
Residue 115: the 'disordered' region

Full EML1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EML1 p.Ala292Val Uncertain significance ★★ ⚠ same type
EML1 p.Arg192His Uncertain significance ★★ ⚠ same type
EML1 p.Arg450Gln Uncertain significance ★★ ⚠ same type
EML1 p.Arg813His Uncertain significance ★★ ⚠ same type
EML1 p.Cys369Phe Uncertain significance ★★ ⚠ same type
EML1 p.Gln409Glu Uncertain significance ★★ ⚠ same type
EML1 p.His351Gln Uncertain significance ★★ ⚠ same type
EML1 p.Val253Met 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/eml1-p-ser115 (accessed [today's date]).

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