Is CYFIP2 p.Asp991= (c.2973C>T) pathogenic?

CYFIP2 p.Asp991= (c.2973C>T) is classified Likely benign in CYFIP2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-06). Ultra-rare (popmax 0.0401%, afr); Associated with Inborn genetic diseases.

What condition is associated with CYFIP2 p.Asp991= (c.2973C>T)?

CYFIP2 p.Asp991= (c.2973C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CYFIP2 p.Asp991= (c.2973C>T) in the general population?

CYFIP2 p.Asp991= (c.2973C>T) is ultra-rare (popmax 0.0401%, afr) (gnomAD).

CYFIP2 p.Asp991=

c.2973C>T · rs775531019 · VCV1619700

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0401%, afr)

Conditions

Inborn genetic diseases

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 -8.3	GERP -3.9
Overall
CADD	2.752	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0401% African / African-American · 30/74,898 alleles

Filtering AF 0.0288% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0249%

Overall 0.00316% 51/1,613,946 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0401%	2,497
South Asian	0.00329%	30,357
East Asian	0.00223%	44,882
Admixed American	0.00167%	59,998
Remaining individualsnot grpmax-eligible	0.0016%	62,480
European (non-Finnish)	0.00127%	78,668

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.Asp991=
Coding: c.2973C>T
MANE Select: NM_001037333
dbSNP: rs775531019
Type: single nucleotide variant
Location: chr5:157361532 (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-asp991 (accessed [today's date]).

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