Is ILF3 p.Ala686Val (c.2057C>T) pathogenic?

ILF3 p.Ala686Val (c.2057C>T) is classified Uncertain significance in ILF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-02). AlphaMissense: ambiguous (0.487); Ultra-rare (popmax 0.0111%, eas).

How common is ILF3 p.Ala686Val (c.2057C>T) in the general population?

ILF3 p.Ala686Val (c.2057C>T) is ultra-rare (popmax 0.0111%, eas) (gnomAD).

What do computational predictors say about ILF3 p.Ala686Val (c.2057C>T)?

AlphaMissense predicts ambiguous (score 0.487) — an in-silico prediction, not a clinical call.

ILF3 p.Ala686Val

c.2057C>T · VCV4678742

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.487 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.487	ambiguous
REVEL	0.116	moderately benign-leaning
SaProt	LLR -8.29	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.5, phastCons 1
Overall
CADD	24.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A682V vs ClinVar A686V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0111% East Asian · 5/44,896 alleles

Filtering AF 0.00434% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.0013% 21/1,613,972 alleles · ultra-rare exomes 19/1,461,814 · genomes 2/152,158 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0111%	8,979
Remaining individualsnot grpmax-eligible	0.0064%	15,620
South Asian	0.00439%	22,770
African / African-American	0.00267%	37,446
Finnishnot grpmax-eligible	0.00156%	64,018
European (non-Finnish)	0.000424%	235,999

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: ILF3
Protein: p.Ala686Val
Coding: c.2057C>T
MANE Select: NM_017620
Type: single nucleotide variant
Location: chr19:10683956 (GRCh38)
Gene constraint: LOEUF 0.309 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 67.74 · 4 PDB
Residue 682 UniProt numbering: the 'interaction with prmt1' region

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-ala686val (accessed [today's date]).

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