Is CYFIP2 p.Leu1007Phe (c.3019C>T) pathogenic?

CYFIP2 p.Leu1007Phe (c.3019C>T) is classified Uncertain significance in CYFIP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-01). AlphaMissense: ambiguous (0.4483); Absent from gnomAD v4.1.

How common is CYFIP2 p.Leu1007Phe (c.3019C>T) in the general population?

CYFIP2 p.Leu1007Phe (c.3019C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CYFIP2 p.Leu1007Phe (c.3019C>T)?

AlphaMissense predicts ambiguous (score 0.4483) — an in-silico prediction, not a clinical call.

CYFIP2 p.Leu1007Phe

c.3019C>T · VCV4769965

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4483 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4483	ambiguous
REVEL	0.277	benign-leaning
SaProt	LLR -9.49	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 1.9, phastCons 1
Regional constraint	o/e 0.58	unconstrained · MANE · 33 kb · p 4.7e-16 · regional, not allelic
Overall
CADD	25.1	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 L1032F vs ClinVar L1007F) — verify the residue.

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: CYFIP2
Protein: p.Leu1007Phe
Coding: c.3019C>T
MANE Select: NM_001037333
Type: single nucleotide variant
Location: chr5:157361578 (GRCh38)
Gene constraint: LOEUF 0.274 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 87.28

Full CYFIP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CYFIP2 p.Arg87Cys Pathogenic/Likely pathogenic ★★ same type
CYFIP2 p.Arg87Pro Pathogenic/Likely pathogenic ★★ same type
CYFIP2 p.Glu640Lys Pathogenic ★★ same type
CYFIP2 p.Tyr108His Likely pathogenic ★★ ⚠ same type
CYFIP2 p.Ala1074Thr Uncertain significance ★★ ⚠ same type
CYFIP2 p.Ala773Thr Uncertain significance ★★ ⚠ same type
CYFIP2 p.Ala80Val Uncertain significance ★★ ⚠ same type
CYFIP2 p.Arg1041His 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/cyfip2-p-leu1007phe (accessed [today's date]).

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