Is ILF3 p.Val227Asp (c.680T>A) pathogenic?

ILF3 p.Val227Asp (c.680T>A) is classified Uncertain significance in ILF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-08). AlphaMissense: likely pathogenic (0.9997); Absent from gnomAD v4.1.

How common is ILF3 p.Val227Asp (c.680T>A) in the general population?

ILF3 p.Val227Asp (c.680T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ILF3 p.Val227Asp (c.680T>A)?

AlphaMissense predicts likely pathogenic (score 0.9997) — an in-silico prediction, not a clinical call.

ILF3 p.Val227Asp

c.680T>A · VCV4678749

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9997 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9997	likely pathogenic · top 6% in ILF3
REVEL	0.581	indeterminate
SaProt	LLR -16.51	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.7, phastCons 1
Overall
CADD	26.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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: ILF3
Protein: p.Val227Asp
Coding: c.680T>A
MANE Select: NM_017620
Type: single nucleotide variant
Location: chr19:10679125 (GRCh38)
Gene constraint: LOEUF 0.309 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 67.74 · 4 PDB
Residue 227: the dzf domain

Full ILF3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ILF3 p.Arg655= Benign ★★ same type
ILF3 p.Ala123Thr Uncertain significance ★ ⚠ same type
ILF3 p.Ala268Val Uncertain significance ★ ⚠ same type
ILF3 p.Ala397Ser Uncertain significance ★ ⚠ same type
ILF3 p.Ala488Thr Uncertain significance ★ ⚠ same type
ILF3 p.Ala494Val Uncertain significance ★ ⚠ same type
ILF3 p.Ala507Val Uncertain significance ★ ⚠ same type
ILF3 p.Ala515Val 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/ilf3-p-val227asp (accessed [today's date]).

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