Is ELFN1 p.Val528Asp (c.1583T>A) pathogenic?

ELFN1 p.Val528Asp (c.1583T>A) is classified Uncertain significance in ELFN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-26). AlphaMissense: likely pathogenic (0.763); Absent from gnomAD v4.1.

How common is ELFN1 p.Val528Asp (c.1583T>A) in the general population?

ELFN1 p.Val528Asp (c.1583T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ELFN1 p.Val528Asp (c.1583T>A)?

AlphaMissense predicts likely pathogenic (score 0.763) — an in-silico prediction, not a clinical call.

ELFN1 p.Val528Asp

c.1583T>A · VCV4663835

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.763 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt

Computational evidence

Protein change
AlphaMissense	0.763	likely pathogenic
SaProt	LLR -7.96	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.3, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 1,744 bp · p 0.16 · regional, not allelic
Overall
CADD	24.8	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: ELFN1
Protein: p.Val528Asp
Coding: c.1583T>A
MANE Select: NM_001128636
Type: single nucleotide variant
Location: chr7:1746179 (GRCh38)
Gene constraint: LOEUF 1.841 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.62 · 5 PDB
Residue 528: the 'disordered' region

Full ELFN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ELFN1 p.Ala14= Benign/Likely benign ★★ same type
ELFN1 p.Ala796= Benign/Likely benign ★★ same type
ELFN1 p.Asp618= Likely benign ★★ same type
ELFN1 p.Cys196= Likely benign ★★ same type
ELFN1 p.Glu258= Benign/Likely benign ★★ same type
ELFN1 p.Gly228= Benign/Likely benign ★★ same type
ELFN1 p.His20= Benign/Likely benign ★★ same type
ELFN1 p.Pro614= Benign/Likely benign ★★ 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/elfn1-p-val528asp (accessed [today's date]).

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