Is CEP68 p.Arg424Trp (c.1270C>T) pathogenic?

CEP68 p.Arg424Trp (c.1270C>T) is classified Likely benign in CEP68 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-13). AlphaMissense: likely benign (0.0605); Rare (popmax 0.105%, sas).

How common is CEP68 p.Arg424Trp (c.1270C>T) in the general population?

CEP68 p.Arg424Trp (c.1270C>T) is rare (popmax 0.105%, sas) (gnomAD).

What do computational predictors say about CEP68 p.Arg424Trp (c.1270C>T)?

AlphaMissense predicts likely benign (score 0.0605) — an in-silico prediction, not a clinical call.

CEP68 p.Arg424Trp

c.1270C>T · rs577037216 · VCV3142989

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0605 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.105%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0605	likely benign
REVEL	0.01	strongly benign-leaning
SaProt	LLR -7.90	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 -1.8	GERP -3.7
Regional constraint	o/e 1.01	unconstrained · MANE · 13 kb · p 0.74 · regional, not allelic
Overall
CADD	0.552	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 0.105% South Asian · 96/91,072 alleles

Filtering AF 0.0883% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0819%

Overall 0.0131% 212/1,613,840 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.105%	949
Middle Eastern	0.066%	1,516
Admixed American	0.0383%	2,610
Remaining individualsnot grpmax-eligible	0.0208%	4,808
European (non-Finnish)	0.00593%	16,857
African / African-American	0.00533%	18,758
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
East Asian	0.00223%	44,862

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: CEP68
Protein: p.Arg424Trp
Coding: c.1270C>T
MANE Select: NM_015147
dbSNP: rs577037216
Type: single nucleotide variant
Location: chr2:65072366 (GRCh38)
Gene constraint: LOEUF 0.627 · pLI 0.05 (gnomAD)
Structure: AlphaFold pLDDT 49.36
Residue 424: the 'disordered' region

Full CEP68 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CEP68 p.Arg424Gln Uncertain significance ★ ⚠ same residue
CEP68 c.2007+9C>G Benign ★★ same type
CEP68 p.Arg217His Benign ★★ same type
CEP68 p.His566= Benign/Likely benign ★★ same type
CEP68 p.Phe367Tyr Benign ★★ same type
CEP68 p.Ser447= Benign ★★ same type
CEP68 p.Val607Ala Benign ★★ same type
CEP68 p.Ala163Thr 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/cep68-p-arg424trp (accessed [today's date]).

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