Is CFAP43 p.Pro641Leu (c.1922C>T) pathogenic?

CFAP43 p.Pro641Leu (c.1922C>T) is classified Uncertain significance in CFAP43 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-04). AlphaMissense: likely benign (0.1132); Very rare (popmax 0.00962%, nfe).

How common is CFAP43 p.Pro641Leu (c.1922C>T) in the general population?

CFAP43 p.Pro641Leu (c.1922C>T) is very rare (popmax 0.00962%, nfe) (gnomAD).

What do computational predictors say about CFAP43 p.Pro641Leu (c.1922C>T)?

AlphaMissense predicts likely benign (score 0.1132) — an in-silico prediction, not a clinical call.

CFAP43 p.Pro641Leu

c.1922C>T · VCV3832284

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1132 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00962%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1132	likely benign
REVEL	0.1	moderately benign-leaning
SaProt	LLR -6.74	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 5.6	GERP 0.99, phastCons 0.99
Regional constraint	o/e 0.92	unconstrained · MANE · 91 kb · p 0.0013 · regional, not allelic
Overall
CADD	17.56	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 0.00962% European (non-Finnish) · 113/1,174,404 alleles

Filtering AF 0.00813% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00764%

Overall 0.00734% 117/1,594,902 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00962%	10,393
Remaining individualsnot grpmax-eligible	0.00325%	30,783
African / African-American	0.00272%	36,775

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: CFAP43
Protein: p.Pro641Leu
Coding: c.1922C>T
MANE Select: NM_025145
Type: single nucleotide variant
Location: chr10:104186062 (GRCh38)
Gene constraint: LOEUF 0.78 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.27 · 1 PDB

Full CFAP43 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CFAP43 p.Arg894Ter Pathogenic/Likely pathogenic ★★ same type
CFAP43 p.Thr1075Lys Uncertain significance ★★ ⚠ same type
CFAP43 c.2142-4A>G Benign ★★ same type
CFAP43 p.Glu1540Gly Benign/Likely benign ★★ same type
CFAP43 p.Leu1542Val Benign/Likely benign ★★ same type
CFAP43 p.Leu616Phe Benign ★★ ⚠ same type
CFAP43 p.Leu802= Benign ★★ same type
CFAP43 p.Pro246= Benign ★★ 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/cfap43-p-pro641leu (accessed [today's date]).

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