Is CYFIP2 p.Phe820= (c.2460C>T) pathogenic?

CYFIP2 p.Phe820= (c.2460C>T) is classified Likely benign in CYFIP2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-05-13). Very rare (popmax 0.00288%, nfe).

How common is CYFIP2 p.Phe820= (c.2460C>T) in the general population?

CYFIP2 p.Phe820= (c.2460C>T) is very rare (popmax 0.00288%, nfe) (gnomAD).

CYFIP2 p.Phe820=

c.2460C>T · rs761084028 · VCV1618062

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00288%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.3	GERP -4.2
Overall
CADD	7.394	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00288% European (non-Finnish) · 34/1,179,896 alleles

Filtering AF 0.00207% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00183%

Overall 0.00254% 41/1,613,902 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0048%	20,822
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
Finnishnot grpmax-eligible	0.00312%	32,005
European (non-Finnish)grpmax	0.00288%	34,703
African / African-American	0.00133%	74,934

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CYFIP2
Protein: p.Phe820=
Coding: c.2460C>T
MANE Select: NM_001037333
dbSNP: rs761084028
Type: single nucleotide variant
Location: chr5:157339131 (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-phe820 (accessed [today's date]).

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