Is CYFIP2 p.Arg548Trp (c.1642C>T) pathogenic?

CYFIP2 p.Arg548Trp (c.1642C>T) is classified Uncertain significance in CYFIP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-29). AlphaMissense: likely pathogenic (0.866); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CYFIP2 p.Arg548Trp (c.1642C>T)?

CYFIP2 p.Arg548Trp (c.1642C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CYFIP2 p.Arg548Trp (c.1642C>T) in the general population?

CYFIP2 p.Arg548Trp (c.1642C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CYFIP2 p.Arg548Trp (c.1642C>T)?

AlphaMissense predicts likely pathogenic (score 0.866) — an in-silico prediction, not a clinical call.

CYFIP2 p.Arg548Trp

c.1642C>T · VCV3498985

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.866 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,606,296)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.866	likely pathogenic
REVEL	0.478	indeterminate
SaProt	LLR -5.14	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 2.1, phastCons 1
Regional constraint	o/e 0.49	unconstrained · MANE · 11 kb · p 1.8e-21 · regional, not allelic
Overall
CADD	32.0	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

No allele count reported in gnomAD v4.1 (AN 1,606,296). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CYFIP2
Protein: p.Arg548Trp
Coding: c.1642C>T
MANE Select: NM_001037333
Type: single nucleotide variant
Location: chr5:157320773 (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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CYFIP2 p.Glu640Lys Pathogenic ★★ same condition
CYFIP2 p.Ala1074Thr Uncertain significance ★★ ⚠ same condition
CYFIP2 p.Arg1041His Uncertain significance ★★ ⚠ same condition
CYFIP2 p.Arg1098His Uncertain significance ★★ ⚠ same condition
CYFIP2 p.Arg1098Leu Uncertain significance ★★ ⚠ same condition
CYFIP2 p.Arg1100Trp Uncertain significance ★★ ⚠ same condition
CYFIP2 p.Arg1206Trp Uncertain significance ★★ ⚠ same condition
CYFIP2 p.Arg1239His Uncertain significance ★★ ⚠ same condition

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-arg548trp (accessed [today's date]).

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