Is CEP112 p.Val470Ile (c.1408G>A) pathogenic?

CEP112 p.Val470Ile (c.1408G>A) is classified Likely benign in CEP112 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-30). AlphaMissense: likely benign (0.071); Ultra-rare (popmax 0.012%, afr).

How common is CEP112 p.Val470Ile (c.1408G>A) in the general population?

CEP112 p.Val470Ile (c.1408G>A) is ultra-rare (popmax 0.012%, afr) (gnomAD).

What do computational predictors say about CEP112 p.Val470Ile (c.1408G>A)?

AlphaMissense predicts likely benign (score 0.071) — an in-silico prediction, not a clinical call.

CEP112 p.Val470Ile

c.1408G>A · VCV3265971

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.071 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.012%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.071	likely benign
REVEL	0.046	moderately benign-leaning
SaProt	LLR -5.71	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 -1.2	GERP -3.6
Regional constraint	o/e 0.99	unconstrained · MANE · 547 kb · p 0.71 · regional, not allelic
Overall
CADD	0.809	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 0.012% African / African-American · 9/74,824 alleles

Filtering AF 0.00624% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00468%

Overall 0.000559% 9/1,611,326 alleles · ultra-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: CEP112
Protein: p.Val470Ile
Coding: c.1408G>A
MANE Select: NM_001199165
Type: single nucleotide variant
Location: chr17:66029218 (GRCh38)
Gene constraint: LOEUF 0.91 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.22
Residue 470: a UniProt-annotated variant site (in spgf44; likely pathogenic); a UniProt-annotated variant site (in spgf44; likely pathogenic; no protein detected in patient cells)

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

Similar variants

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
CEP112 p.Ala401Val 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-val470ile (accessed [today's date]).

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