Is ESPL1 p.Ser39= (c.117C>T) pathogenic?

ESPL1 p.Ser39= (c.117C>T) is classified Likely benign in ESPL1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-03-25). Very rare (popmax 0.0011%, sas); Associated with ESPL1-related disorder.

What condition is associated with ESPL1 p.Ser39= (c.117C>T)?

ESPL1 p.Ser39= (c.117C>T) is associated with ESPL1-related disorder (ClinVar).

How common is ESPL1 p.Ser39= (c.117C>T) in the general population?

ESPL1 p.Ser39= (c.117C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

ESPL1 p.Ser39=

c.117C>T · rs768270715 · VCV3058575

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

ESPL1-related disorder

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 -0.026	GERP 2.1, phastCons 0.027
Overall
CADD	10.38	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/90,972 alleles

Overall 0.000205% 3/1,460,886 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,480
South Asiangrpmax	0.0011%	90,972
European (non-Finnish)	8.48e-05%	1,179,496

Remaining individuals 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: ESPL1
Protein: p.Ser39=
Coding: c.117C>T
MANE Select: NM_012291
dbSNP: rs768270715
Type: single nucleotide variant
Location: chr12:53269059 (GRCh38)
Gene constraint: LOEUF 0.292 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 75.67 · 9 PDB

Full ESPL1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ESPL1-related disorder

Similar variants

ESPL1 p.Ser39Asn Uncertain significance ★ ⚠ same residue
ESPL1 p.Ser1239Ter Uncertain significance ★ same condition
ESPL1 c.6161+7C>T Likely benign same condition
ESPL1 p.Ala116Val Benign ⚠ same condition
ESPL1 p.Ala1438= Likely benign same condition
ESPL1 p.Arg1318Gln Likely benign same condition
ESPL1 p.Asn1723= Likely benign same condition
ESPL1 p.Asp1351= Likely benign same condition

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/espl1-p-ser39 (accessed [today's date]).

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