Is CEP112 p.Arg431Ser (c.1293G>T) pathogenic?

CEP112 p.Arg431Ser (c.1293G>T) is classified Uncertain significance in CEP112 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-21). AlphaMissense: ambiguous (0.4336); Absent from gnomAD v4.1.

How common is CEP112 p.Arg431Ser (c.1293G>T) in the general population?

CEP112 p.Arg431Ser (c.1293G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CEP112 p.Arg431Ser (c.1293G>T)?

AlphaMissense predicts ambiguous (score 0.4336) — an in-silico prediction, not a clinical call.

CEP112 p.Arg431Ser

c.1293G>T · VCV4000542

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4336 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4336	ambiguous
REVEL	0.071	moderately benign-leaning
SaProt	LLR -7.42	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.54	GERP -0.75, phastCons 0.019
Regional constraint	o/e 0.99	unconstrained · MANE · 547 kb · p 0.71 · regional, not allelic
Overall
CADD	13.94	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CEP112
Protein: p.Arg431Ser
Coding: c.1293G>T
MANE Select: NM_001199165
Type: single nucleotide variant
Location: chr17:66029949 (GRCh38)
Gene constraint: LOEUF 0.91 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.22
Residue 431: 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-arg431ser (accessed [today's date]).

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