Is CFP p.Pro204Leu (c.611C>T) pathogenic?

CFP p.Pro204Leu (c.611C>T) is classified Benign/Likely benign in CFP (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-06). AlphaMissense: likely benign (0.0841); Low-frequency (popmax 2.37%, afr).

How common is CFP p.Pro204Leu (c.611C>T) in the general population?

CFP p.Pro204Leu (c.611C>T) is low-frequency (popmax 2.37%, afr) (gnomAD).

What do computational predictors say about CFP p.Pro204Leu (c.611C>T)?

AlphaMissense predicts likely benign (score 0.0841) — an in-silico prediction, not a clinical call.

CFP p.Pro204Leu

c.611C>T · rs8177076 · VCV729229

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0841 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.37%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0841	likely benign
REVEL	0.031	moderately benign-leaning
SaProt	LLR -8.04	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 4.3	GERP 0.56, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 5,566 bp · p 3.9e-05 · regional, not allelic
Overall
CADD	15.52	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

Grpmax group 2.37% African / African-American · 1,363/57,454 alleles

Filtering AF 2.27% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.23%

Overall 0.134% 1,615/1,202,522 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.37%	42
Admixed American	0.234%	428
Remaining individualsnot grpmax-eligible	0.21%	477
Middle Eastern	0.185%	540
European (non-Finnish)	0.00416%	24,064
South Asian	0.00359%	27,825

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.Pro204Leu
Coding: c.611C>T
MANE Select: NM_001145252
dbSNP: rs8177076
Type: single nucleotide variant
Location: chrX:47627296 (GRCh38)
Structure: AlphaFold pLDDT 83.75 · 14 PDB
Residue 204: the tsp type-1 3 domain; a UniProt-annotated variant site (in); an α-helix

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

Similar variants

CFP p.Pro204Arg Uncertain significance ★★ ⚠ same residue
CFP p.Pro204= Likely benign ★ same residue
CFP p.Trp321Gly Pathogenic ★★ same type
CFP p.Ala402Gly Uncertain significance ★★ ⚠ same type
CFP p.Arg157Gln Uncertain significance ★★ ⚠ same type
CFP p.Arg157Trp Uncertain significance ★★ ⚠ same type
CFP p.Arg159Cys Uncertain significance ★★ ⚠ same type
CFP p.Arg247Trp 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/cfp-p-pro204leu (accessed [today's date]).

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