Is CFAP52 p.Val67Ile (c.199G>A) pathogenic?

CFAP52 p.Val67Ile (c.199G>A) is classified Uncertain significance in CFAP52 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-12). AlphaMissense: likely benign (0.0855); Ultra-rare (popmax 0.029%, eas); Associated with situs inversus.

What condition is associated with CFAP52 p.Val67Ile (c.199G>A)?

CFAP52 p.Val67Ile (c.199G>A) is associated with situs inversus (ClinVar).

How common is CFAP52 p.Val67Ile (c.199G>A) in the general population?

CFAP52 p.Val67Ile (c.199G>A) is ultra-rare (popmax 0.029%, eas) (gnomAD).

What do computational predictors say about CFAP52 p.Val67Ile (c.199G>A)?

AlphaMissense predicts likely benign (score 0.0855) — an in-silico prediction, not a clinical call.

CFAP52 p.Val67Ile

c.199G>A · rs201479202 · VCV544338

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0855 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.029%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

situs inversus

Computational evidence

Protein change
AlphaMissense	0.0855	likely benign
REVEL	0.199	benign-leaning
SaProt	LLR -5.42	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 2.3	GERP 1.9, phastCons 0.99
Regional constraint	o/e 1.00	unconstrained · MANE · 66 kb · p 0.9 · regional, not allelic
Overall
CADD	16.07	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 0.029% East Asian · 13/44,832 alleles

Filtering AF 0.0171% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.00235% 38/1,613,748 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.029%	3,449
African / African-American	0.00934%	10,703
South Asian	0.00659%	15,176
Admixed American	0.00167%	59,972
Remaining individualsnot grpmax-eligible	0.0016%	62,500
European (non-Finnish)	0.000847%	117,997

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: CFAP52
Protein: p.Val67Ile
Coding: c.199G>A
MANE Select: NM_145054
dbSNP: rs201479202
Type: single nucleotide variant
Location: chr17:9585901 (GRCh38)
Gene constraint: LOEUF 1.022 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.59 · 2 PDB

Full CFAP52 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

situs inversus — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CFAP52 p.Ala147Thr Uncertain significance ★★ ⚠ same condition
CFAP52 p.Ala161Asp Uncertain significance ★★ ⚠ same condition
CFAP52 p.Arg170Gln Uncertain significance ★★ ⚠ same condition
CFAP52 p.Arg594Cys Uncertain significance ★★ ⚠ same condition
CFAP52 p.Gly343Ser Uncertain significance ★★ ⚠ same condition
CFAP52 p.Gly534Ala Uncertain significance ★★ same condition
CFAP52 p.Met551Thr Uncertain significance ★★ ⚠ same condition
CFAP52 p.Tyr41His Uncertain significance ★★ same condition

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/cfap52-p-val67ile (accessed [today's date]).

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