Is CEP68 p.Phe367Tyr (c.1100T>A) pathogenic?

CEP68 p.Phe367Tyr (c.1100T>A) is classified Benign in CEP68 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). AlphaMissense: likely benign (0.1423); Low-frequency (popmax 1.65%, nfe).

How common is CEP68 p.Phe367Tyr (c.1100T>A) in the general population?

CEP68 p.Phe367Tyr (c.1100T>A) is low-frequency (popmax 1.65%, nfe) (gnomAD).

What do computational predictors say about CEP68 p.Phe367Tyr (c.1100T>A)?

AlphaMissense predicts likely benign (score 0.1423) — an in-silico prediction, not a clinical call.

CEP68 p.Phe367Tyr

c.1100T>A · rs141499084 · VCV788725

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1423 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.65%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1423	likely benign
REVEL	0.036	moderately benign-leaning
SaProt	LLR -7.34	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 0.27	GERP -0.25, phastCons 0.86
Regional constraint	o/e 1.01	unconstrained · MANE · 13 kb · p 0.74 · regional, not allelic
Overall
CADD	17.81	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 1.65% European (non-Finnish) · 19,460/1,179,974 alleles

Filtering AF 1.63% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.62%

Overall 1.39% 22,512/1,614,036 alleles · low-frequency

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	2.99%	33
European (non-Finnish)grpmax	1.65%	61
Amishnot grpmax-eligible	1.65%	61
Remaining individualsnot grpmax-eligible	1.27%	79
Finnishnot grpmax-eligible	1.16%	86
Admixed American	0.447%	224
African / African-American	0.293%	341
Middle Eastern	0.165%	606
South Asian	0.13%	772

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: CEP68
Protein: p.Phe367Tyr
Coding: c.1100T>A
MANE Select: NM_015147
dbSNP: rs141499084
Type: single nucleotide variant
Location: chr2:65072196 (GRCh38)
Gene constraint: LOEUF 0.627 · pLI 0.05 (gnomAD)
Structure: AlphaFold pLDDT 49.36
Residue 367: the 'disordered' region

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

Similar variants

CEP68 c.2007+9C>G Benign ★★ same type
CEP68 p.Arg217His Benign ★★ same type
CEP68 p.His566= Benign/Likely benign ★★ same type
CEP68 p.Ser447= Benign ★★ same type
CEP68 p.Val607Ala Benign ★★ same type
CEP68 p.Ala163Thr Uncertain significance ★ ⚠ same type
CEP68 p.Ala214Val Uncertain significance ★ ⚠ same type
CEP68 p.Ala325Val 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-phe367tyr (accessed [today's date]).

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