Is CEP72 p.Ala421Val (c.1262C>T) pathogenic?

CEP72 p.Ala421Val (c.1262C>T) is classified Uncertain significance in CEP72 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-07). AlphaMissense: likely benign (0.0968); Ultra-rare (popmax 0.0494%, sas).

How common is CEP72 p.Ala421Val (c.1262C>T) in the general population?

CEP72 p.Ala421Val (c.1262C>T) is ultra-rare (popmax 0.0494%, sas) (gnomAD).

What do computational predictors say about CEP72 p.Ala421Val (c.1262C>T)?

AlphaMissense predicts likely benign (score 0.0968) — an in-silico prediction, not a clinical call.

CEP72 p.Ala421Val

c.1262C>T · rs760155795 · VCV2283925

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0968 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0494%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0968	likely benign
REVEL	0.008	strongly benign-leaning
SaProt	LLR -6.72	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 -1.7	GERP -4.5
Regional constraint	o/e 1.10	unconstrained · MANE · 41 kb · p 0.005 · regional, not allelic
Overall
CADD	1.648	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 0.0494% South Asian · 45/91,052 alleles

Filtering AF 0.0379% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0339%

Overall 0.0036% 58/1,612,818 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0494%	2,023
Remaining individualsnot grpmax-eligible	0.0032%	31,229
East Asian	0.00223%	44,874
Finnishnot grpmax-eligible	0.00158%	63,350
European (non-Finnish)	0.000763%	131,074

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: CEP72
Protein: p.Ala421Val
Coding: c.1262C>T
MANE Select: NM_018140
dbSNP: rs760155795
Type: single nucleotide variant
Location: chr5:639144 (GRCh38)
Gene constraint: LOEUF 1.409 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.74

Full CEP72 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CEP72 p.Ala192Val Uncertain significance ★★ ⚠ same type
CEP72 p.Asp135= Benign ★★ same type
TPPP p.Ala148= Likely benign ★★ same type
TPPP p.His207= Benign ★★ same type
TPPP p.Thr167= Benign ★★ same type
CEP72 p.Ala17Gly Uncertain significance ★ ⚠ same type
CEP72 p.Ala2Gly Uncertain significance ★ ⚠ same type
CEP72 p.Ala386Val 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/cep72-p-ala421val (accessed [today's date]).

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