Is CFAP99 p.Arg513His (c.1538G>A) pathogenic?

CFAP99 p.Arg513His (c.1538G>A) is classified Uncertain significance in CFAP99 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-02). Ultra-rare (popmax 0.0843%, amr).

How common is CFAP99 p.Arg513His (c.1538G>A) in the general population?

CFAP99 p.Arg513His (c.1538G>A) is ultra-rare (popmax 0.0843%, amr) (gnomAD).

CFAP99 p.Arg513His

c.1538G>A · rs112369376 · VCV2358723

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0843%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.059	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.3	GERP 0.55, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 36 kb · p 0.016 · regional, not allelic
Overall
CADD	21.3	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0843% Admixed American · 43/50,998 alleles

Filtering AF 0.0643% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0573%

Overall 0.0162% 249/1,536,106 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.356%	281
Admixed Americangrpmax	0.0843%	1,186
Remaining individualsnot grpmax-eligible	0.04%	2,500
African / African-American	0.0109%	9,146
South Asian	0.00833%	12,009
European (non-Finnish)	0.00549%	18,205
East Asian	0.00244%	40,912
Finnishnot grpmax-eligible	0.00225%	44,498

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CFAP99
Protein: p.Arg513His
Coding: c.1538G>A
MANE Select: NM_001193282
dbSNP: rs112369376
Type: single nucleotide variant
Location: chr4:2460119 (GRCh38)
Gene constraint: LOEUF 1.203 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.28

Full CFAP99 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CFAP99 p.Arg513Cys Uncertain significance ★ same residue
CFAP99 p.Ala255Thr Uncertain significance ★ same type
CFAP99 p.Ala307Thr Uncertain significance ★ same type
CFAP99 p.Ala366Thr Uncertain significance ★ same type
CFAP99 p.Ala369Gly Uncertain significance ★ same type
CFAP99 p.Ala396Val Uncertain significance ★ same type
CFAP99 p.Ala423Thr Uncertain significance ★ same type
CFAP99 p.Ala428Thr Uncertain significance ★ 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/cfap99-p-arg513his (accessed [today's date]).

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