Is ESPL1 p.Ala1438= (c.4314C>T) pathogenic?

ESPL1 p.Ala1438= (c.4314C>T) is classified Likely benign in ESPL1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-12-02). Rare (popmax 0.1%, eas); Associated with ESPL1-related disorder.

What condition is associated with ESPL1 p.Ala1438= (c.4314C>T)?

ESPL1 p.Ala1438= (c.4314C>T) is associated with ESPL1-related disorder (ClinVar).

How common is ESPL1 p.Ala1438= (c.4314C>T) in the general population?

ESPL1 p.Ala1438= (c.4314C>T) is rare (popmax 0.1%, eas) (gnomAD).

ESPL1 p.Ala1438=

c.4314C>T · rs192407973 · VCV3048978

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.1%, eas)

Conditions

ESPL1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.48 · evaluated, not missing
Constraint at this position
Conservation	phyloP -10	GERP -3.8
Overall
CADD	1.7	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.1% East Asian · 45/44,876 alleles

Filtering AF 0.077% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0688%

Overall 0.00768% 124/1,613,668 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.1%	997
Remaining individualsnot grpmax-eligible	0.024%	4,165
African / African-American	0.012%	8,339
South Asian	0.011%	9,105
European (non-Finnish)	0.00381%	26,222

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.Ala1438=
Coding: c.4314C>T
MANE Select: NM_012291
dbSNP: rs192407973
Type: single nucleotide variant
Location: chr12:53288109 (GRCh38)
Gene constraint: LOEUF 0.292 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 75.67 · 9 PDB
Residue 1438: the 'disordered' region

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

Disease context

ESPL1-related disorder

Similar variants

ESPL1 p.Ser1239Ter Uncertain significance ★ same condition
ESPL1 c.6161+7C>T Likely benign same condition
ESPL1 p.Ala116Val Benign ⚠ same condition
ESPL1 p.Arg1318Gln Likely benign same condition
ESPL1 p.Asn1723= Likely benign same condition
ESPL1 p.Asp1351= Likely benign same condition
ESPL1 p.Gly1510Arg Likely benign same condition
ESPL1 p.His1078Asn 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-ala1438 (accessed [today's date]).

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