Is CENPC p.Arg248Gln (c.743G>A) pathogenic?

CENPC p.Arg248Gln (c.743G>A) is classified Likely benign in CENPC (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-16). AlphaMissense: likely benign (0.0642); Very rare (popmax 0.00194%, amr).

How common is CENPC p.Arg248Gln (c.743G>A) in the general population?

CENPC p.Arg248Gln (c.743G>A) is very rare (popmax 0.00194%, amr) (gnomAD).

What do computational predictors say about CENPC p.Arg248Gln (c.743G>A)?

AlphaMissense predicts likely benign (score 0.0642) — an in-silico prediction, not a clinical call.

CENPC p.Arg248Gln

c.743G>A · rs2545840381 · VCV3142270

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0642 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00194%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0642	likely benign
REVEL	0.03	moderately benign-leaning
SaProt	LLR -5.69	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 3.4	GERP -0.29, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 73 kb · p 0.0018 · regional, not allelic
Overall
CADD	7.493	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 0.00194% Admixed American · 1/51,596 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000213% 3/1,407,506 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00194%	51,596
European (non-Finnish)	0.000174%	576,190

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: CENPC
Protein: p.Arg248Gln
Coding: c.743G>A
MANE Select: NM_001812
dbSNP: rs2545840381
Type: single nucleotide variant
Location: chr4:67518243 (GRCh38)
Gene constraint: LOEUF 0.886 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 48.33 · 17 PDB
Residue 248: the 'disordered' region

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

Similar variants

CENPC p.Ala165Thr Uncertain significance ★ ⚠ same type
CENPC p.Ala23Val Uncertain significance ★ ⚠ same type
CENPC p.Ala313Val Uncertain significance ★ ⚠ same type
CENPC p.Ala324Thr Uncertain significance ★ ⚠ same type
CENPC p.Ala783Glu Uncertain significance ★ ⚠ same type
CENPC p.Ala783Thr Uncertain significance ★ ⚠ same type
CENPC p.Arg24His Uncertain significance ★ ⚠ same type
CENPC p.Arg272Gln 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/cenpc-p-arg248gln (accessed [today's date]).

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