Is CFAP43 p.Leu616Phe (c.1846C>T) pathogenic?

CFAP43 p.Leu616Phe (c.1846C>T) is classified Benign in CFAP43 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). AlphaMissense: likely benign (0.0897); Low-frequency (popmax 3.94%, afr).

How common is CFAP43 p.Leu616Phe (c.1846C>T) in the general population?

CFAP43 p.Leu616Phe (c.1846C>T) is low-frequency (popmax 3.94%, afr) (gnomAD).

What do computational predictors say about CFAP43 p.Leu616Phe (c.1846C>T)?

AlphaMissense predicts likely benign (score 0.0897) — an in-silico prediction, not a clinical call.

CFAP43 p.Leu616Phe

c.1846C>T · rs35901897 · VCV716309

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0897 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.94%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0897	likely benign
REVEL	0.012	strongly benign-leaning
SaProt	LLR -7.80	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 0.32	GERP -3.6
Regional constraint	o/e 0.92	unconstrained · MANE · 91 kb · p 0.0013 · regional, not allelic
Overall
CADD	2.582	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 3.94% African / African-American · 2,898/73,640 alleles

Filtering AF 3.82% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.77%

Overall 0.203% 3,232/1,592,808 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.94%	25
Remaining individualsnot grpmax-eligible	0.261%	383
Admixed American	0.253%	395
Middle Eastern	0.1%	997
South Asian	0.0116%	8,630
European (non-Finnish)	0.00187%	53,377

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.Leu616Phe
Coding: c.1846C>T
MANE Select: NM_025145
dbSNP: rs35901897
Type: single nucleotide variant
Location: chr10:104187334 (GRCh38)
Gene constraint: LOEUF 0.78 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.27 · 1 PDB
Residue 616: a UniProt-annotated variant site (in)

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.Leu802= Benign ★★ same type
CFAP43 p.Pro246= Benign ★★ same type
CFAP43 p.Ser296= 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-leu616phe (accessed [today's date]).

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