Is CEP68 p.Ala344Val (c.1031C>T) pathogenic?

CEP68 p.Ala344Val (c.1031C>T) is classified Uncertain significance in CEP68 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-11). AlphaMissense: likely benign (0.1517); Very rare (popmax 8.47e-05%, nfe).

How common is CEP68 p.Ala344Val (c.1031C>T) in the general population?

CEP68 p.Ala344Val (c.1031C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about CEP68 p.Ala344Val (c.1031C>T)?

AlphaMissense predicts likely benign (score 0.1517) — an in-silico prediction, not a clinical call.

CEP68 p.Ala344Val

c.1031C>T · VCV3490889

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1517 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1517	likely benign
REVEL	0.106	moderately benign-leaning
SaProt	LLR -7.16	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.36	donor gain · deltas
Pangolin	Δ0.23	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 5	GERP 2.1, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 13 kb · p 0.74 · regional, not allelic
Overall
CADD	28.8	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 8.47e-05% European (non-Finnish) · 1/1,180,020 alleles

Overall 6.84e-05% 1/1,461,892 alleles · very rare

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.Ala344Val
Coding: c.1031C>T
MANE Select: NM_015147
Type: single nucleotide variant
Location: chr2:65072127 (GRCh38)
Gene constraint: LOEUF 0.627 · pLI 0.05 (gnomAD)
Structure: AlphaFold pLDDT 49.36
Residue 344: 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.Phe367Tyr 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

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-ala344val (accessed [today's date]).

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