Is CEP68 p.Arg322His (c.965G>A) pathogenic?

CEP68 p.Arg322His (c.965G>A) is classified Likely benign in CEP68 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-20). AlphaMissense: likely benign (0.0605); Ultra-rare (popmax 0.0165%, mid).

How common is CEP68 p.Arg322His (c.965G>A) in the general population?

CEP68 p.Arg322His (c.965G>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about CEP68 p.Arg322His (c.965G>A)?

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

CEP68 p.Arg322His

c.965G>A · VCV3490882

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

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0605	likely benign
REVEL	0.036	moderately benign-leaning
SaProt	LLR -7.18	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 -1.6	GERP -4.3
Regional constraint	o/e 1.01	unconstrained · MANE · 13 kb · p 0.74 · regional, not allelic
Overall
CADD	3.364	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 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.00435% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.0031% 50/1,613,830 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
East Asian	0.0111%	8,969
Remaining individualsnot grpmax-eligible	0.008%	12,500
Admixed American	0.00333%	29,997
South Asian	0.00329%	30,357
European (non-Finnish)	0.00288%	34,705

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.Arg322His
Coding: c.965G>A
MANE Select: NM_015147
Type: single nucleotide variant
Location: chr2:65072061 (GRCh38)
Gene constraint: LOEUF 0.627 · pLI 0.05 (gnomAD)
Structure: AlphaFold pLDDT 49.36
Residue 322: the 'disordered' region

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

Similar variants

CEP68 p.Arg322Cys Uncertain significance ★ ⚠ same residue
CEP68 p.Arg322Leu 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

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-arg322his (accessed [today's date]).

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