Is CFI p.Gly263Ser (c.787G>A) pathogenic?

CFI p.Gly263Ser (c.787G>A) is classified Conflicting classifications of pathogenicity in CFI (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-04-01). AlphaMissense: likely benign (0.058); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CFI p.Gly263Ser (c.787G>A)?

CFI p.Gly263Ser (c.787G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CFI p.Gly263Ser (c.787G>A) in the general population?

CFI p.Gly263Ser (c.787G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CFI p.Gly263Ser (c.787G>A)?

AlphaMissense predicts likely benign (score 0.058) — an in-silico prediction, not a clinical call.

CFI p.Gly263Ser

c.787G>A · VCV3617764

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.058 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,936)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.058	likely benign
REVEL	0.303	indeterminate
SaProt	LLR -4.94	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.3	GERP -3.3
Regional constraint	o/e 1.00	unconstrained · MANE · 61 kb · p 0.95 · regional, not allelic
Overall
CADD	0.182	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 1,613,936). 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: CFI
Protein: p.Gly263Ser
Coding: c.787G>A
MANE Select: NM_000204
Type: single nucleotide variant
Location: chr4:109760366 (GRCh38)
Gene constraint: LOEUF 1.076 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.50 · 2 PDB
Residue 263: a disulfide bond; the ldl-receptor class a 2 domain

Full CFI 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

CFI p.Gly263Val Uncertain significance ★★ ⚠ same residue
CFI p.Gly263fs Pathogenic ★★ same residue
CFI p.Ala511Val Uncertain significance ★★ ⚠ same condition
CFI p.Asn102Ser Uncertain significance ★★ ⚠ same condition
CFI p.Glu109Lys Uncertain significance ★★ ⚠ same condition
CFI p.Glu445Asp Uncertain significance ★★ ⚠ same condition
CFI p.His401Gln Uncertain significance ★★ ⚠ same condition
CFI p.Ile126Thr 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/cfi-p-gly263ser (accessed [today's date]).

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