Is ESPL1 p.Val103Asp (c.308T>A) pathogenic?

ESPL1 p.Val103Asp (c.308T>A) is classified Uncertain significance in ESPL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-14). AlphaMissense: likely pathogenic (0.8712); Absent from gnomAD v4.1.

How common is ESPL1 p.Val103Asp (c.308T>A) in the general population?

ESPL1 p.Val103Asp (c.308T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ESPL1 p.Val103Asp (c.308T>A)?

AlphaMissense predicts likely pathogenic (score 0.8712) — an in-silico prediction, not a clinical call.

ESPL1 p.Val103Asp

c.308T>A · VCV4251076

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8712 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8712	likely pathogenic · top 6% in ESPL1
REVEL	0.152	moderately benign-leaning
SaProt	LLR -6.43	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 14 kb · p 6.3e-24 · regional, not allelic
Overall
CADD	23.7	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ESPL1
Protein: p.Val103Asp
Coding: c.308T>A
MANE Select: NM_012291
Type: single nucleotide variant
Location: chr12:53269250 (GRCh38)
Gene constraint: LOEUF 0.292 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 75.67 · 9 PDB
Residue 103: an α-helix

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

Similar variants

ESPL1 c.6162-10C>T Benign ★★ same type
ESPL1 p.Ala1462Thr Benign ★★ same type
ESPL1 p.Asn918Ser Benign ★★ same type
ESPL1 p.Gly1337Val Benign ★★ same type
ESPL1 p.Ile1488Asn Benign ★★ same type
ESPL1 p.Ser969= Benign ★★ same type
ESPL1 p.Thr2073Met Likely benign ★★ ⚠ same type
ESPL1 c.5241+1G>A 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/espl1-p-val103asp (accessed [today's date]).

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