Is CEP112 p.Ala78Val (c.233C>T) pathogenic?

CEP112 p.Ala78Val (c.233C>T) is classified Likely benign in CEP112 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-10). AlphaMissense: likely benign (0.0496); Ultra-rare (popmax 0.0314%, nfe).

How common is CEP112 p.Ala78Val (c.233C>T) in the general population?

CEP112 p.Ala78Val (c.233C>T) is ultra-rare (popmax 0.0314%, nfe) (gnomAD).

What do computational predictors say about CEP112 p.Ala78Val (c.233C>T)?

AlphaMissense predicts likely benign (score 0.0496) — an in-silico prediction, not a clinical call.

CEP112 p.Ala78Val

c.233C>T · rs150126064 · VCV2384846

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0496 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0314%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0496	likely benign
REVEL	0.124	moderately benign-leaning
SaProt	LLR -4.03	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.36 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1	GERP -2.3
Regional constraint	o/e 0.99	unconstrained · MANE · 547 kb · p 0.71 · regional, not allelic
Overall
CADD	5.922	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 0.0314% European (non-Finnish) · 370/1,179,834 alleles

Filtering AF 0.0287% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0277%

Overall 0.0253% 408/1,613,538 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0314%	3,189
Remaining individualsnot grpmax-eligible	0.0288%	3,470
African / African-American	0.0174%	5,756
Finnishnot grpmax-eligible	0.00625%	15,993
Admixed American	0.00334%	29,969
South Asian	0.0011%	91,034

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: CEP112
Protein: p.Ala78Val
Coding: c.233C>T
MANE Select: NM_001199165
dbSNP: rs150126064
Type: single nucleotide variant
Location: chr17:66176894 (GRCh38)
Gene constraint: LOEUF 0.91 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.22
Residue 78: a UniProt-annotated variant site (in spgf44; likely pathogenic)

Full CEP112 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CEP112 p.Ala78Glu Uncertain significance ★ ⚠ same residue
CEP112 p.Lys139Arg Uncertain significance ★★ ⚠ same type
CEP112 p.Lys569Asn Uncertain significance ★★ ⚠ same type
CEP112 p.Leu937= Benign ★★ same type
CEP112 c.955+1G>A Likely pathogenic ★ same type
CEP112 p.Gln418Ter Likely pathogenic ★ same type
CEP112 p.Ala338Val Uncertain significance ★ ⚠ same type
CEP112 p.Ala401Gly 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/cep112-p-ala78val (accessed [today's date]).

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