Is EML1 p.Ser295= (c.885G>A) pathogenic?

EML1 p.Ser295= (c.885G>A) is classified Likely benign in EML1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-02-26). Ultra-rare (popmax 0.021%, sas).

How common is EML1 p.Ser295= (c.885G>A) in the general population?

EML1 p.Ser295= (c.885G>A) is ultra-rare (popmax 0.021%, sas) (gnomAD).

EML1 p.Ser295=

c.885G>A · rs369951654 · VCV2415815

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.021%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.145	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.8	GERP -3.8
Overall
CADD	7.893	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.021% South Asian · 19/90,588 alleles

Filtering AF 0.0137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0114%

Overall 0.0109% 176/1,611,090 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.196%	509
South Asiangrpmax	0.021%	4,768
Middle Eastern	0.0166%	6,040
Remaining individualsnot grpmax-eligible	0.016%	6,233
European (non-Finnish)	0.00687%	14,546
African / African-American	0.00667%	14,996
East Asian	0.00223%	44,838
Admixed American	0.00167%	59,702

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser295=
Coding: c.885G>A
MANE Select: NM_004434
dbSNP: rs369951654
Type: single nucleotide variant
Location: chr14:99898290 (GRCh38)
Gene constraint: LOEUF 0.36 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 86.49 · 1 PDB
Residue 295: the 'tandem atypical propeller in emls' region

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

Similar variants

EML1 p.Ser295Leu Uncertain significance ★ ⚠ same residue
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

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-ser295 (accessed [today's date]).

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