Is CEP44 p.Phe85Leu (c.253T>C) pathogenic?

CEP44 p.Phe85Leu (c.253T>C) is classified Uncertain significance in CEP44 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-24). AlphaMissense: likely pathogenic (0.9864); Absent from gnomAD v4.1.

How common is CEP44 p.Phe85Leu (c.253T>C) in the general population?

CEP44 p.Phe85Leu (c.253T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CEP44 p.Phe85Leu (c.253T>C)?

AlphaMissense predicts likely pathogenic (score 0.9864) — an in-silico prediction, not a clinical call.

CEP44 p.Phe85Leu

c.253T>C · rs2477325335 · VCV2297077

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9864 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,532,938)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9864	likely pathogenic · top 2% in CEP44
REVEL	0.445	indeterminate
SaProt	LLR -7.17	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 18 kb · p 0.48 · regional, not allelic
Overall
CADD	27.0	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

No allele count reported in gnomAD v4.1 (AN 1,532,938). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CEP44
Protein: p.Phe85Leu
Coding: c.253T>C
MANE Select: NM_001040157
dbSNP: rs2477325335
Type: single nucleotide variant
Location: chr4:174303718 (GRCh38)
Gene constraint: LOEUF 1.34 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.41 · 1 PDB
Residue 85: the 'binds with microtubules and centrioles' region

Full CEP44 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CEP44 p.Ala102Gly Uncertain significance ★ ⚠ same type
CEP44 p.Ala155Thr Uncertain significance ★ ⚠ same type
CEP44 p.Ala172Ser Uncertain significance ★ ⚠ same type
CEP44 p.Ala172Thr Uncertain significance ★ ⚠ same type
CEP44 p.Ala172Val Uncertain significance ★ ⚠ same type
CEP44 p.Ala349Gly Uncertain significance ★ ⚠ same type
CEP44 p.Arg11Gln Uncertain significance ★ ⚠ same type
CEP44 p.Arg176Cys 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/cep44-p-phe85leu (accessed [today's date]).

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