Is CFP p.Val53Met (c.157G>A) pathogenic?

CFP p.Val53Met (c.157G>A) is classified Benign/Likely benign in CFP (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-03). AlphaMissense: likely benign (0.0841); Rare (popmax 0.809%, afr).

How common is CFP p.Val53Met (c.157G>A) in the general population?

CFP p.Val53Met (c.157G>A) is rare (popmax 0.809%, afr) (gnomAD).

What do computational predictors say about CFP p.Val53Met (c.157G>A)?

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

CFP p.Val53Met

c.157G>A · rs8177068 · VCV728910

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0841 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.809%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0841	likely benign
REVEL	0.008	strongly benign-leaning
SaProt	LLR -8.24	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.92	GERP -0.56
Regional constraint	o/e 0.79	unconstrained · MANE · 5,566 bp · p 3.9e-05 · regional, not allelic
Overall
CADD	5.483	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 0.809% African / African-American · 449/55,531 alleles

Filtering AF 0.747% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.722%

Overall 0.0454% 530/1,167,272 alleles · rare exomes 245/1,058,251 · genomes 285/109,021 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.809%	124
Admixed American	0.0775%	1,290
Remaining individualsnot grpmax-eligible	0.0739%	1,353
East Asian	0.00629%	15,907
Ashkenazi Jewishnot grpmax-eligible	0.00471%	21,226
European (non-Finnish)	0.0016%	62,350

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.Val53Met
Coding: c.157G>A
MANE Select: NM_001145252
dbSNP: rs8177068
Type: single nucleotide variant
Location: chrX:47629594 (GRCh38)
Structure: AlphaFold pLDDT 83.75 · 14 PDB
Residue 53: the tsp type-1 0 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.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-val53met (accessed [today's date]).

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