Is CFAP36 p.Glu104Ala (c.311A>C) pathogenic?

CFAP36 p.Glu104Ala (c.311A>C) is classified Uncertain significance in CFAP36 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-07). AlphaMissense: likely pathogenic (0.7149); Ultra-rare (popmax 0.0157%, nfe).

How common is CFAP36 p.Glu104Ala (c.311A>C) in the general population?

CFAP36 p.Glu104Ala (c.311A>C) is ultra-rare (popmax 0.0157%, nfe) (gnomAD).

What do computational predictors say about CFAP36 p.Glu104Ala (c.311A>C)?

AlphaMissense predicts likely pathogenic (score 0.7149) — an in-silico prediction, not a clinical call.

CFAP36 p.Glu104Ala

c.311A>C · rs191927946 · VCV2459739

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7149 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0157%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7149	likely pathogenic
REVEL	0.208	benign-leaning
SaProt	LLR -7.23	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 1.3, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 25 kb · p 0.59 · regional, not allelic
Overall
CADD	25.0	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 0.0157% European (non-Finnish) · 185/1,177,902 alleles

Filtering AF 0.0138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0131%

Overall 0.0129% 208/1,609,032 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0157%	6,367
Admixed American	0.0135%	7,398
Remaining individualsnot grpmax-eligible	0.0128%	7,790
East Asian	0.00671%	14,905
Finnishnot grpmax-eligible	0.00469%	21,337
South Asian	0.00112%	89,538

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.Glu104Ala
Coding: c.311A>C
MANE Select: NM_080667
dbSNP: rs191927946
Type: single nucleotide variant
Location: chr2:55528906 (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.Arg21Pro 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

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-glu104ala (accessed [today's date]).

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