Is CFAP36 p.Arg21Pro (c.62G>C) pathogenic?

CFAP36 p.Arg21Pro (c.62G>C) is classified Uncertain significance in CFAP36 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-10). AlphaMissense: likely pathogenic (0.9555); Ultra-rare (popmax 0.0107%, afr).

How common is CFAP36 p.Arg21Pro (c.62G>C) in the general population?

CFAP36 p.Arg21Pro (c.62G>C) is ultra-rare (popmax 0.0107%, afr) (gnomAD).

What do computational predictors say about CFAP36 p.Arg21Pro (c.62G>C)?

AlphaMissense predicts likely pathogenic (score 0.9555) — an in-silico prediction, not a clinical call.

CFAP36 p.Arg21Pro

c.62G>C · VCV4652807

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9555 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0107%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9555	likely pathogenic · top 8% in CFAP36
REVEL	0.203	benign-leaning
SaProt	LLR -12.59	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.5	GERP 2.2, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 25 kb · p 0.59 · regional, not allelic
Overall
CADD	26.0	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 0.0107% African / African-American · 8/74,940 alleles

Filtering AF 0.00528% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.00062% 10/1,614,116 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0107%	9,368
Remaining individualsnot grpmax-eligible	0.0032%	31,242

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: CFAP36
Protein: p.Arg21Pro
Coding: c.62G>C
MANE Select: NM_080667
Type: single nucleotide variant
Location: chr2:55519863 (GRCh38)
Gene constraint: LOEUF 0.867 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.92

Full CFAP36 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CFAP36 p.Ala332Thr Uncertain significance ★ ⚠ same type
CFAP36 p.Arg126Gln Uncertain significance ★ ⚠ same type
CFAP36 p.Arg176Thr Uncertain significance ★ ⚠ same type
CFAP36 p.Arg280Thr Uncertain significance ★ ⚠ same type
CFAP36 p.Arg328Lys Uncertain significance ★ ⚠ same type
CFAP36 p.Asn132Ser Uncertain significance ★ ⚠ same type
CFAP36 p.Asp144Asn Uncertain significance ★ ⚠ same type
CFAP36 p.Asp281Tyr 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/cfap36-p-arg21pro (accessed [today's date]).

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