Is CFAP43 p.Ser1001Phe (c.3002C>T) pathogenic?

CFAP43 p.Ser1001Phe (c.3002C>T) is classified Uncertain significance in CFAP43 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-15). AlphaMissense: ambiguous (0.3736); Very rare (popmax 0.00668%, afr).

How common is CFAP43 p.Ser1001Phe (c.3002C>T) in the general population?

CFAP43 p.Ser1001Phe (c.3002C>T) is very rare (popmax 0.00668%, afr) (gnomAD).

What do computational predictors say about CFAP43 p.Ser1001Phe (c.3002C>T)?

AlphaMissense predicts ambiguous (score 0.3736) — an in-silico prediction, not a clinical call.

CFAP43 p.Ser1001Phe

c.3002C>T · VCV3266433

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3736 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, afr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3736	ambiguous
REVEL	0.271	benign-leaning
SaProt	LLR -10.42	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 2, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 91 kb · p 0.0013 · regional, not allelic
Overall
CADD	26.1	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 0.00668% African / African-American · 5/74,884 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00162%

Overall 0.000496% 8/1,613,712 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00668%	14,977
Admixed American	0.00333%	29,991
Remaining individualsnot grpmax-eligible	0.0016%	62,470

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.Ser1001Phe
Coding: c.3002C>T
MANE Select: NM_025145
Type: single nucleotide variant
Location: chr10:104166525 (GRCh38)
Gene constraint: LOEUF 0.78 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.27 · 1 PDB
Residue 1001: a UniProt-annotated variant site (in spgf19)

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-ser1001phe (accessed [today's date]).

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