Is CYFIP1 p.Gln915Glu (c.2743C>G) pathogenic?

CYFIP1 p.Gln915Glu (c.2743C>G) is classified Uncertain significance in CYFIP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-31). AlphaMissense: likely benign (0.1022); Very rare (popmax 0.00668%, eas).

How common is CYFIP1 p.Gln915Glu (c.2743C>G) in the general population?

CYFIP1 p.Gln915Glu (c.2743C>G) is very rare (popmax 0.00668%, eas) (gnomAD).

What do computational predictors say about CYFIP1 p.Gln915Glu (c.2743C>G)?

AlphaMissense predicts likely benign (score 0.1022) — an in-silico prediction, not a clinical call.

CYFIP1 p.Gln915Glu

c.2743C>G · rs1417228805 · VCV2532162

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1022 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt

Computational evidence

Protein change
AlphaMissense	0.1022	likely benign
SaProt	LLR -6.14	tolerated
⇒ AlphaMissense and SaProt both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 0.76, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 57 kb · p 5.3e-08 · regional, not allelic
Overall
CADD	20.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00668% East Asian · 3/44,892 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00108%

Overall 0.0018% 29/1,613,972 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00668%	14,964
European (non-Finnish)	0.00195%	51,303
Admixed American	0.00167%	59,992
Remaining individualsnot grpmax-eligible	0.0016%	62,490
South Asian	0.0011%	91,084

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: CYFIP1
Protein: p.Gln915Glu
Coding: c.2743C>G
MANE Select: NM_014608
dbSNP: rs1417228805
Type: single nucleotide variant
Location: chr15:22882945 (GRCh38)
Gene constraint: LOEUF 0.44 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 90.24 · 5 PDB
Residue 915: an α-helix

Full CYFIP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CYFIP1 p.Gln915Lys Uncertain significance ★ ⚠ same residue
CYFIP1 p.Phe600Leu Uncertain significance ★★ ⚠ same type
CYFIP1 c.3043-4C>G Benign/Likely benign ★★ same type
CYFIP1 p.Ala1003Val Benign ★★ same type
CYFIP1 p.Ala385Thr Benign ★★ same type
CYFIP1 p.Glu347= Benign ★★ same type
CYFIP1 p.Gly903Ser Benign/Likely benign ★★ same type
CYFIP1 p.Ile795Val Benign ★★ 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/cyfip1-p-gln915glu (accessed [today's date]).

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