Is CEP76 p.Phe511Ile (c.1531T>A) pathogenic?

CEP76 p.Phe511Ile (c.1531T>A) is classified Conflicting classifications of pathogenicity in CEP76 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-07-02). AlphaMissense: likely benign (0.144); Very rare (popmax 0.00686%, nfe).

How common is CEP76 p.Phe511Ile (c.1531T>A) in the general population?

CEP76 p.Phe511Ile (c.1531T>A) is very rare (popmax 0.00686%, nfe) (gnomAD).

What do computational predictors say about CEP76 p.Phe511Ile (c.1531T>A)?

AlphaMissense predicts likely benign (score 0.144) — an in-silico prediction, not a clinical call.

CEP76 p.Phe511Ile

c.1531T>A · VCV4075836

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.144 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00686%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.144	likely benign
REVEL	0.189	benign-leaning
SaProt	LLR -1.14	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 11	GERP 1.6, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 29 kb · p 0.00019 · regional, not allelic
Overall
CADD	21.7	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 0.00686% European (non-Finnish) · 81/1,180,012 alleles

Filtering AF 0.00563% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00515%

Overall 0.0052% 84/1,614,058 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00686%	14,568
Remaining individualsnot grpmax-eligible	0.0032%	31,244
Finnishnot grpmax-eligible	0.00156%	64,040

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: CEP76
Protein: p.Phe511Ile
Coding: c.1531T>A
MANE Select: NM_024899
Type: single nucleotide variant
Location: chr18:12678201 (GRCh38)
Gene constraint: LOEUF 0.716 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.18

Full CEP76 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CEP76 p.Arg568Pro Likely pathogenic ★ same type
CEP76 p.Cys478Arg Likely pathogenic ★ same type
CEP76 p.Ile101Thr Likely pathogenic ★ ⚠ same type
CEP76 p.Leu166Pro Likely pathogenic ★ same type
CEP76 p.Lys374= Pathogenic ★ same type
CEP76 p.Pro103Ser Pathogenic ★ ⚠ same type
CEP76 p.Val24Asp Likely pathogenic ★ same type
CEP76 p.Val265Met Likely pathogenic ★ ⚠ 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/cep76-p-phe511ile (accessed [today's date]).

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