Is CEP112 p.Arg253Cys (c.757C>T) pathogenic?

CEP112 p.Arg253Cys (c.757C>T) is classified Uncertain significance in CEP112 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-20). AlphaMissense: likely benign (0.09); Very rare (popmax 0.00502%, amr).

How common is CEP112 p.Arg253Cys (c.757C>T) in the general population?

CEP112 p.Arg253Cys (c.757C>T) is very rare (popmax 0.00502%, amr) (gnomAD).

What do computational predictors say about CEP112 p.Arg253Cys (c.757C>T)?

AlphaMissense predicts likely benign (score 0.09) — an in-silico prediction, not a clinical call.

CEP112 p.Arg253Cys

c.757C>T · VCV3265969

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.09 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00502%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.09	likely benign
REVEL	0.155	moderately benign-leaning
SaProt	LLR -7.27	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.41 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6.5	GERP 0.35, phastCons 1
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 0.00502% Admixed American · 3/59,814 alleles

Filtering AF 0.00173% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0015%

Overall 0.00242% 39/1,609,328 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00502%	19,938
South Asian	0.00441%	22,684
Remaining individualsnot grpmax-eligible	0.00321%	31,151
European (non-Finnish)	0.00246%	40,576
African / African-American	0.00134%	74,748

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.Arg253Cys
Coding: c.757C>T
MANE Select: NM_001199165
Type: single nucleotide variant
Location: chr17:66096262 (GRCh38)
Gene constraint: LOEUF 0.91 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.22
Residue 253: 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-arg253cys (accessed [today's date]).

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