Is CFP p.Lys66Gln (c.196A>C) pathogenic?

CFP p.Lys66Gln (c.196A>C) is classified Uncertain significance in CFP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-30). AlphaMissense: likely benign (0.0739); Absent from gnomAD v4.1.

How common is CFP p.Lys66Gln (c.196A>C) in the general population?

CFP p.Lys66Gln (c.196A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CFP p.Lys66Gln (c.196A>C)?

AlphaMissense predicts likely benign (score 0.0739) — an in-silico prediction, not a clinical call.

CFP p.Lys66Gln

c.196A>C · VCV3665477

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0739 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0739	likely benign
REVEL	0.059	moderately benign-leaning
SaProt	LLR -5.69	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 -0.42	GERP -3.2, phastCons 0.001
Regional constraint	o/e 0.79	unconstrained · MANE · 5,566 bp · p 3.9e-05 · regional, not allelic
Overall
CADD	0.275	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CFP
Protein: p.Lys66Gln
Coding: c.196A>C
MANE Select: NM_001145252
Type: single nucleotide variant
Location: chrX:47629555 (GRCh38)
Structure: AlphaFold pLDDT 83.75 · 14 PDB
Residue 66: the tsp type-1 0 domain; a disulfide bond; a β-strand

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

Similar variants

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
CFP p.Arg438Trp Uncertain significance ★★ ⚠ same type
CFP p.Asn307Ser 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-lys66gln (accessed [today's date]).

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