Is CFAP43 p.Met693Val (c.2077A>G) pathogenic?

CFAP43 p.Met693Val (c.2077A>G) is classified Uncertain significance in CFAP43 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-21). AlphaMissense: likely benign (0.0685); Very rare (popmax 0.00668%, eas).

How common is CFAP43 p.Met693Val (c.2077A>G) in the general population?

CFAP43 p.Met693Val (c.2077A>G) is very rare (popmax 0.00668%, eas) (gnomAD).

What do computational predictors say about CFAP43 p.Met693Val (c.2077A>G)?

AlphaMissense predicts likely benign (score 0.0685) — an in-silico prediction, not a clinical call.

CFAP43 p.Met693Val

c.2077A>G · rs1241680251 · VCV3143459

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0685 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0685	likely benign
REVEL	0.049	moderately benign-leaning
SaProt	LLR -0.79	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 -4.4	GERP -3.4
Regional constraint	o/e 0.92	unconstrained · MANE · 91 kb · p 0.0013 · regional, not allelic
Overall
CADD	0.102	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 0.00668% East Asian · 3/44,886 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000434% 7/1,614,046 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00668%	14,962
African / African-American	0.00534%	18,732

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.Met693Val
Coding: c.2077A>G
MANE Select: NM_025145
dbSNP: rs1241680251
Type: single nucleotide variant
Location: chr10:104185080 (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-met693val (accessed [today's date]).

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