Is CEP20 p.Arg116Cys (c.346C>T) pathogenic?

CEP20 p.Arg116Cys (c.346C>T) is classified Uncertain significance in CEP20 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-04-18). AlphaMissense: likely benign (0.0839); Very rare (popmax 0.00549%, sas).

How common is CEP20 p.Arg116Cys (c.346C>T) in the general population?

CEP20 p.Arg116Cys (c.346C>T) is very rare (popmax 0.00549%, sas) (gnomAD).

What do computational predictors say about CEP20 p.Arg116Cys (c.346C>T)?

AlphaMissense predicts likely benign (score 0.0839) — an in-silico prediction, not a clinical call.

CEP20 p.Arg116Cys

c.346C>T · VCV4000823

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0839 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00549%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0839	likely benign
REVEL	0.086	moderately benign-leaning
SaProt	LLR -9.59	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.32 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.5	GERP 0.3, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 21 kb · p 0.34 · regional, not allelic
Overall
CADD	26.0	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 0.00549% South Asian · 5/91,068 alleles

Filtering AF 0.0021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.00192% 31/1,613,674 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00549%	18,214
Admixed American	0.00333%	29,986
Remaining individualsnot grpmax-eligible	0.0032%	31,235
European (non-Finnish)	0.00178%	56,182
African / African-American	0.00134%	74,894

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: CEP20
Protein: p.Arg116Cys
Coding: c.346C>T
MANE Select: NM_144600
Type: single nucleotide variant
Location: chr16:15873593 (GRCh38)
Gene constraint: LOEUF 1.579 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.95

Full CEP20 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CEP20 p.Ala2Gly Uncertain significance ★ ⚠ same type
CEP20 p.Ala2Val Uncertain significance ★ ⚠ same type
CEP20 p.Ala30Val Uncertain significance ★ ⚠ same type
CEP20 p.Ala35Thr Uncertain significance ★ ⚠ same type
CEP20 p.Ala70Thr Uncertain significance ★ ⚠ same type
CEP20 p.Arg141Ser Uncertain significance ★ ⚠ same type
CEP20 p.Arg40Cys Uncertain significance ★ ⚠ same type
CEP20 p.Arg43Pro 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/cep20-p-arg116cys (accessed [today's date]).

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