Is CFP p.Gly200Asp (c.599G>A) pathogenic?

CFP p.Gly200Asp (c.599G>A) is classified Uncertain significance in CFP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-01-16). AlphaMissense: likely benign (0.208); Very rare (popmax 0.000225%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CFP p.Gly200Asp (c.599G>A)?

CFP p.Gly200Asp (c.599G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CFP p.Gly200Asp (c.599G>A) in the general population?

CFP p.Gly200Asp (c.599G>A) is very rare (popmax 0.000225%, nfe) (gnomAD).

What do computational predictors say about CFP p.Gly200Asp (c.599G>A)?

AlphaMissense predicts likely benign (score 0.208) — an in-silico prediction, not a clinical call.

CFP p.Gly200Asp

c.599G>A · rs2519717142 · VCV2781821

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.208 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000225%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.208	likely benign
REVEL	0.284	benign-leaning
SaProt	LLR -8.43	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP -0.53, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 5,566 bp · p 3.9e-05 · regional, not allelic
Overall
CADD	19.94	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 0.000225% European (non-Finnish) · 2/887,854 alleles

Filtering AF 3.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.4e-05%

Overall 0.000184% 2/1,084,793 alleles · very rare

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: CFP
Protein: p.Gly200Asp
Coding: c.599G>A
MANE Select: NM_001145252
dbSNP: rs2519717142
Type: single nucleotide variant
Location: chrX:47627308 (GRCh38)
Structure: AlphaFold pLDDT 83.75 · 14 PDB
Residue 200: the tsp type-1 3 domain

Full CFP 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

CFP p.Ala402Gly Uncertain significance ★★ ⚠ same condition
CFP p.Arg157Trp Uncertain significance ★★ ⚠ same condition
CFP p.Arg438Trp Uncertain significance ★★ ⚠ same condition
CFP p.Asn307Ser Uncertain significance ★★ ⚠ same condition
CFP p.Glu215Lys Uncertain significance ★★ ⚠ same condition
CFP p.Lys413Glu Uncertain significance ★★ ⚠ same condition
CFP p.Phe431Val Uncertain significance ★★ ⚠ same condition
CFP p.Pro204Arg 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/cfp-p-gly200asp (accessed [today's date]).

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