Is CEP112 p.Val722Phe (c.2164G>T) pathogenic?

CEP112 p.Val722Phe (c.2164G>T) is classified Uncertain significance in CEP112 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-11). AlphaMissense: likely benign (0.1464); Very rare (popmax 0.000255%, nfe).

How common is CEP112 p.Val722Phe (c.2164G>T) in the general population?

CEP112 p.Val722Phe (c.2164G>T) is very rare (popmax 0.000255%, nfe) (gnomAD).

What do computational predictors say about CEP112 p.Val722Phe (c.2164G>T)?

AlphaMissense predicts likely benign (score 0.1464) — an in-silico prediction, not a clinical call.

CEP112 p.Val722Phe

c.2164G>T · VCV3490456

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1464 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000255%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1464	likely benign
REVEL	0.1	moderately benign-leaning
SaProt	LLR -8.31	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 0.36	GERP 0.61, phastCons 0.98
Regional constraint	o/e 0.99	unconstrained · MANE · 547 kb · p 0.71 · regional, not allelic
Overall
CADD	24.2	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 0.000255% European (non-Finnish) · 3/1,174,602 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000251% 4/1,595,856 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00162%	61,696
European (non-Finnish)grpmax	0.000255%	391,533

Remaining individuals 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: CEP112
Protein: p.Val722Phe
Coding: c.2164G>T
MANE Select: NM_001199165
Type: single nucleotide variant
Location: chr17:65852034 (GRCh38)
Gene constraint: LOEUF 0.91 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.22
Residue 722: 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-val722phe (accessed [today's date]).

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