Is CEP128 p.Arg150Trp (c.448C>T) pathogenic?

CEP128 p.Arg150Trp (c.448C>T) is classified Uncertain significance in CEP128 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-07). AlphaMissense: likely benign (0.1308); Ultra-rare (popmax 0.0107%, afr).

How common is CEP128 p.Arg150Trp (c.448C>T) in the general population?

CEP128 p.Arg150Trp (c.448C>T) is ultra-rare (popmax 0.0107%, afr) (gnomAD).

What do computational predictors say about CEP128 p.Arg150Trp (c.448C>T)?

AlphaMissense predicts likely benign (score 0.1308) — an in-silico prediction, not a clinical call.

CEP128 p.Arg150Trp

c.448C>T · VCV3265990

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1308 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0107%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1308	likely benign
REVEL	0.367	indeterminate
SaProt	LLR -9.79	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.31 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 419 kb · p 0.4 · regional, not allelic
Overall
CADD	27.5	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 0.0107% African / African-American · 8/74,682 alleles

Filtering AF 0.00529% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00382%

Overall 0.00765% 123/1,606,998 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.159%	629
Remaining individualsnot grpmax-eligible	0.0177%	5,661
African / African-Americangrpmax	0.0107%	9,335
Admixed American	0.00667%	14,995
European (non-Finnish)	0.00417%	23,954
East Asian	0.00223%	44,844
South Asian	0.0022%	45,459
Finnishnot grpmax-eligible	0.00156%	64,008

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg150Trp
Coding: c.448C>T
MANE Select: NM_152446
Type: single nucleotide variant
Location: chr14:80904845 (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.Arg150Leu 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-arg150trp (accessed [today's date]).

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