Is CEP112 p.Arg324Cys (c.970C>T) pathogenic?

CEP112 p.Arg324Cys (c.970C>T) is classified Uncertain significance in CEP112 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-23). AlphaMissense: likely benign (0.2425); Ultra-rare (popmax 0.0627%, eas).

How common is CEP112 p.Arg324Cys (c.970C>T) in the general population?

CEP112 p.Arg324Cys (c.970C>T) is ultra-rare (popmax 0.0627%, eas) (gnomAD).

What do computational predictors say about CEP112 p.Arg324Cys (c.970C>T)?

AlphaMissense predicts likely benign (score 0.2425) — an in-silico prediction, not a clinical call.

CEP112 p.Arg324Cys

c.970C>T · rs573903382 · VCV2569042

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2425 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0627%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2425	likely benign
REVEL	0.388	indeterminate
SaProt	LLR -7.71	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.6	GERP 1.6, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 547 kb · p 0.71 · regional, not allelic
Overall
CADD	33.0	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 0.0627% East Asian · 27/43,086 alleles

Filtering AF 0.0441% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0381%

Overall 0.00312% 49/1,573,026 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0627%	1,596
African / African-American	0.00681%	14,684
European (non-Finnish)	0.00138%	72,486
South Asian	0.0012%	83,008

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.Arg324Cys
Coding: c.970C>T
MANE Select: NM_001199165
dbSNP: rs573903382
Type: single nucleotide variant
Location: chr17:66063067 (GRCh38)
Gene constraint: LOEUF 0.91 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.22
Residue 324: 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-arg324cys (accessed [today's date]).

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