Is CENPP p.Ala211Thr (c.631G>A) pathogenic?

CENPP p.Ala211Thr (c.631G>A) is classified Uncertain significance in CENPP (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-27). AlphaMissense: likely benign (0.072); Very rare (popmax 0.00667%, amr).

How common is CENPP p.Ala211Thr (c.631G>A) in the general population?

CENPP p.Ala211Thr (c.631G>A) is very rare (popmax 0.00667%, amr) (gnomAD).

What do computational predictors say about CENPP p.Ala211Thr (c.631G>A)?

AlphaMissense predicts likely benign (score 0.072) — an in-silico prediction, not a clinical call.

CENPP p.Ala211Thr

c.631G>A · rs748491263 · VCV2313752

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.072 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.072	likely benign
REVEL	0.004	strongly benign-leaning
SaProt	LLR -6.30	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.26 · evaluated, not missing
Constraint at this position
Conservation	phyloP -4.9	GERP -4.3
Regional constraint	o/e 0.96	unconstrained · MANE · 287 kb · p 0.47 · regional, not allelic
Overall
CADD	0.098	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 0.00667% Admixed American · 4/59,968 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.00112% 18/1,612,758 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00667%	14,992
South Asian	0.0033%	30,333
European (non-Finnish)	0.000932%	107,262

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: CENPP
Protein: p.Ala211Thr
Coding: c.631G>A
MANE Select: NM_001012267
dbSNP: rs748491263
Type: single nucleotide variant
Location: chr9:92611380 (GRCh38)
Gene constraint: LOEUF 1.272 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 84.96 · 13 PDB

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

Similar variants

CENPP p.Cys283Ter Likely pathogenic ★ same type
CENPP p.Ala17Val Uncertain significance ★ ⚠ same type
CENPP p.Ala258Gly Uncertain significance ★ ⚠ same type
CENPP p.Arg180His Uncertain significance ★ ⚠ same type
CENPP p.Arg209Cys Uncertain significance ★ ⚠ same type
CENPP p.Arg209Gly Uncertain significance ★ ⚠ same type
CENPP p.Arg209His Uncertain significance ★ ⚠ same type
CENPP p.Arg34Gln 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/cenpp-p-ala211thr (accessed [today's date]).

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