Is CEP43 p.Ser27Arg (c.81C>A) pathogenic?

CEP43 p.Ser27Arg (c.81C>A) is classified Uncertain significance in CEP43 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-07). AlphaMissense: likely pathogenic (0.8812); Very rare (popmax 0.00438%, afr).

How common is CEP43 p.Ser27Arg (c.81C>A) in the general population?

CEP43 p.Ser27Arg (c.81C>A) is very rare (popmax 0.00438%, afr) (gnomAD).

What do computational predictors say about CEP43 p.Ser27Arg (c.81C>A)?

AlphaMissense predicts likely pathogenic (score 0.8812) — an in-silico prediction, not a clinical call.

CEP43 p.Ser27Arg

c.81C>A · VCV3266214

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8812 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00438%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8812	likely pathogenic · top 10% in CEP43
REVEL	0.139	moderately benign-leaning
SaProt	LLR -4.66	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 1.7	phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 41 kb · p 0.13 · regional, not allelic
Overall
CADD	23.9	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 0.00438% African / African-American · 3/68,426 alleles

Filtering AF 0.00116% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000623%

Overall 0.000203% 3/1,481,390 alleles · very rare

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: CEP43
Protein: p.Ser27Arg
Coding: c.81C>A
MANE Select: NM_007045
Type: single nucleotide variant
Location: chr6:166999493 (GRCh38)
Gene constraint: LOEUF 1.163 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.69 · 1 PDB

Full CEP43 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CEP43 p.Ala148Val Uncertain significance ★ ⚠ same type
CEP43 p.Ala39Gly Uncertain significance ★ ⚠ same type
CEP43 p.Ala6Val Uncertain significance ★ ⚠ same type
CEP43 p.Ala79Glu Uncertain significance ★ ⚠ same type
CEP43 p.Arg112Gln Uncertain significance ★ ⚠ same type
CEP43 p.Arg134Cys Uncertain significance ★ ⚠ same type
CEP43 p.Arg134Gly Uncertain significance ★ ⚠ same type
CEP43 p.Arg17Trp 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/cep43-p-ser27arg (accessed [today's date]).

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