Is CEP78 p.Ala12Val (c.35C>T) pathogenic?

CEP78 p.Ala12Val (c.35C>T) is classified Benign/Likely benign in CEP78 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-01). AlphaMissense: likely benign (0.1475); Low-frequency (popmax 1.2%, afr).

How common is CEP78 p.Ala12Val (c.35C>T) in the general population?

CEP78 p.Ala12Val (c.35C>T) is low-frequency (popmax 1.2%, afr) (gnomAD).

What do computational predictors say about CEP78 p.Ala12Val (c.35C>T)?

AlphaMissense predicts likely benign (score 0.1475) — an in-silico prediction, not a clinical call.

CEP78 p.Ala12Val

c.35C>T · rs182452644 · VCV731106

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.1475 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.2%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1475	likely benign
REVEL	0.096	moderately benign-leaning
SaProt	LLR -6.42	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 3.1	GERP 0.58, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 34 kb · p 0.014 · regional, not allelic
Overall
CADD	24.7	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 1.2% African / African-American · 898/74,594 alleles

Filtering AF 1.14% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.11%

Overall 0.0707% 1,125/1,590,198 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.2%	83
Ashkenazi Jewishnot grpmax-eligible	0.329%	304
Remaining individualsnot grpmax-eligible	0.104%	963
Admixed American	0.0592%	1,688
Middle Eastern	0.0497%	2,013
European (non-Finnish)	0.00239%	41,797
South Asian	0.00227%	44,048

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: CEP78
Protein: p.Ala12Val
Coding: c.35C>T
MANE Select: NM_001330691
dbSNP: rs182452644
Type: single nucleotide variant
Location: chr9:78236385 (GRCh38)
Gene constraint: LOEUF 1.531 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 64.28

Full CEP78 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CEP78 c.1205+2T>A Pathogenic/Likely pathogenic ★★ same type
CEP78 c.1206-2A>C Pathogenic ★★ same type
CEP78 c.1206-2A>G Pathogenic/Likely pathogenic ★★ same type
CEP78 c.1251+5G>A Pathogenic/Likely pathogenic ★★ same type
CEP78 c.254-1G>T Pathogenic/Likely pathogenic ★★ same type
CEP78 c.778+1G>A Likely pathogenic ★★ same type
CEP78 p.Arg483Ter Pathogenic/Likely pathogenic ★★ same type
CEP78 p.Cys158Phe Pathogenic/Likely pathogenic ★★ 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/cep78-p-ala12val (accessed [today's date]).

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