Is CEP128 p.Arg241His (c.722G>A) pathogenic?

CEP128 p.Arg241His (c.722G>A) is classified Uncertain significance in CEP128 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-14). AlphaMissense: likely benign (0.084); Very rare (popmax 0.00329%, sas).

How common is CEP128 p.Arg241His (c.722G>A) in the general population?

CEP128 p.Arg241His (c.722G>A) is very rare (popmax 0.00329%, sas) (gnomAD).

What do computational predictors say about CEP128 p.Arg241His (c.722G>A)?

AlphaMissense predicts likely benign (score 0.084) — an in-silico prediction, not a clinical call.

CEP128 p.Arg241His

c.722G>A · VCV4225845

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.084 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.084	likely benign
REVEL	0.106	moderately benign-leaning
SaProt	LLR -6.43	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 0.81, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 419 kb · p 0.4 · regional, not allelic
Overall
CADD	23.3	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 0.00329% South Asian · 3/91,070 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000991% 16/1,613,732 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,357
East Asian	0.00223%	44,884
European (non-Finnish)	0.00102%	98,317

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: CEP128
Protein: p.Arg241His
Coding: c.722G>A
MANE Select: NM_152446
Type: single nucleotide variant
Location: chr14:80862797 (GRCh38)
Gene constraint: LOEUF 0.957 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.92

Full CEP128 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CEP128 p.Arg241Pro Uncertain significance ★ ⚠ same residue
TSHR p.Cys29Ter Pathogenic ★★ same type
TSHR p.Cys29Trp Uncertain significance ★★ ⚠ same type
TSHR p.Leu57Pro Uncertain significance ★★ ⚠ same type
CEP128 p.Gln443Arg Likely benign ★★ same type
CEP128 p.Thr317= Benign ★★ same type
TSHR c.170+10C>T Likely benign ★★ same type
TSHR c.170+16A>C Likely benign ★★ 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/cep128-p-arg241his (accessed [today's date]).

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