Is CFAP43 p.Val667Ile (c.1999G>A) pathogenic?

CFAP43 p.Val667Ile (c.1999G>A) is classified Conflicting classifications of pathogenicity in CFAP43 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2022-10-25). AlphaMissense: likely benign (0.0676); Ultra-rare (popmax 0.0201%, eas); Associated with normal pressure hydrocephalus.

What condition is associated with CFAP43 p.Val667Ile (c.1999G>A)?

CFAP43 p.Val667Ile (c.1999G>A) is associated with normal pressure hydrocephalus (ClinVar).

How common is CFAP43 p.Val667Ile (c.1999G>A) in the general population?

CFAP43 p.Val667Ile (c.1999G>A) is ultra-rare (popmax 0.0201%, eas) (gnomAD).

What do computational predictors say about CFAP43 p.Val667Ile (c.1999G>A)?

AlphaMissense predicts likely benign (score 0.0676) — an in-silico prediction, not a clinical call.

CFAP43 p.Val667Ile

c.1999G>A · rs139015694 · VCV2388140

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0676 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0201%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

normal pressure hydrocephalus

Computational evidence

Protein change
AlphaMissense	0.0676	likely benign
REVEL	0.046	moderately benign-leaning
SaProt	LLR -5.86	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 -8.6	GERP -3.8
Regional constraint	o/e 0.92	unconstrained · MANE · 91 kb · p 0.0013 · regional, not allelic
Overall
CADD	0.002	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 0.0201% East Asian · 9/44,740 alleles

Filtering AF 0.0104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00781%

Overall 0.0036% 58/1,611,266 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0201%	4,971
Remaining individualsnot grpmax-eligible	0.00641%	15,594
African / African-American	0.00536%	18,668
South Asian	0.00332%	30,160
European (non-Finnish)	0.00314%	31,871
Admixed American	0.00169%	59,322

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.Val667Ile
Coding: c.1999G>A
MANE Select: NM_025145
dbSNP: rs139015694
Type: single nucleotide variant
Location: chr10:104185985 (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

Disease context

normal pressure hydrocephalus — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CFAP43 p.Thr1075Lys Uncertain significance ★★ ⚠ same condition
CFAP43 p.Arg1313Ter Likely pathogenic ★ same condition
CFAP43 p.Cys44Ser Uncertain significance ★ ⚠ same condition
CFAP43 p.Val905Ala Uncertain significance ★ ⚠ same condition
CFAP43 p.Trp1502Ter Pathogenic same condition
CFAP43 p.Thr1250fs Likely pathogenic ★★ same condition
CFAP43 p.Ser1527fs Likely pathogenic ★ same condition
CFAP43 p.Arg894Ter Pathogenic/Likely pathogenic ★★ 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-val667ile (accessed [today's date]).

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