Is CFAP36 p.Glu307Lys (c.919G>A) pathogenic?

CFAP36 p.Glu307Lys (c.919G>A) is classified Uncertain significance in CFAP36 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-11). AlphaMissense: likely benign (0.0785); Very rare (popmax 0.00134%, afr).

How common is CFAP36 p.Glu307Lys (c.919G>A) in the general population?

CFAP36 p.Glu307Lys (c.919G>A) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about CFAP36 p.Glu307Lys (c.919G>A)?

AlphaMissense predicts likely benign (score 0.0785) — an in-silico prediction, not a clinical call.

CFAP36 p.Glu307Lys

c.919G>A · VCV4001455

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0785 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0785	likely benign
REVEL	0.069	moderately benign-leaning
SaProt	LLR -6.05	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.33	donor gain · deltas
Pangolin	Δ0.35	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 6.8	GERP 1.8, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 25 kb · p 0.59 · regional, not allelic
Overall
CADD	22.3	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 0.00134% African / African-American · 1/74,736 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000248% 4/1,610,642 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,736
European (non-Finnish)	0.000254%	393,026

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.Glu307Lys
Coding: c.919G>A
MANE Select: NM_080667
Type: single nucleotide variant
Location: chr2:55544361 (GRCh38)
Gene constraint: LOEUF 0.867 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.92
Residue 307: the 'disordered' region

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-glu307lys (accessed [today's date]).

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