Is CFP p.Asp299Asn (c.895G>A) pathogenic?

CFP p.Asp299Asn (c.895G>A) is classified Benign/Likely benign in CFP (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-06). AlphaMissense: likely benign (0.0861); Rare (popmax 0.184%, mid).

How common is CFP p.Asp299Asn (c.895G>A) in the general population?

CFP p.Asp299Asn (c.895G>A) is rare (popmax 0.184%, mid) (gnomAD).

What do computational predictors say about CFP p.Asp299Asn (c.895G>A)?

AlphaMissense predicts likely benign (score 0.0861) — an in-silico prediction, not a clinical call.

CFP p.Asp299Asn

c.895G>A · rs61737993 · VCV726140

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.0861 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.184%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0861	likely benign
REVEL	0.167	moderately benign-leaning
SaProt	LLR -5.53	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 7.6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 5,566 bp · p 3.9e-05 · regional, not allelic
Overall
CADD	21.6	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 0.184% Middle Eastern · 8/4,348 alleles

Filtering AF 0.142% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.139%

Overall 0.146% 1,766/1,210,303 alleles · rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	7.81%	13
Finnishnot grpmax-eligible	0.573%	174
Middle Easterngrpmax	0.184%	543
European (non-Finnish)	0.148%	674
Remaining individualsnot grpmax-eligible	0.122%	821
South Asian	0.037%	2,703
Admixed American	0.0305%	3,282
African / African-American	0.0209%	4,793
Ashkenazi Jewishnot grpmax-eligible	0.0182%	5,500

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asp299Asn
Coding: c.895G>A
MANE Select: NM_001145252
dbSNP: rs61737993
Type: single nucleotide variant
Location: chrX:47626818 (GRCh38)
Structure: AlphaFold pLDDT 83.75 · 14 PDB
Residue 299: a disulfide bond; the tsp type-1 4 domain

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-asp299asn (accessed [today's date]).

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