Is CEP164 p.Met183Lys (c.548T>A) pathogenic?

CEP164 p.Met183Lys (c.548T>A) is classified Conflicting classifications of pathogenicity in CEP164 (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2024-10-30). AlphaMissense: likely benign (0.1126); Rare (popmax 0.103%, sas); Associated with Inborn genetic diseases.

What condition is associated with CEP164 p.Met183Lys (c.548T>A)?

CEP164 p.Met183Lys (c.548T>A) is associated with Inborn genetic diseases, nephronophthisis 15, inherited retinal dystrophy (ClinVar).

How common is CEP164 p.Met183Lys (c.548T>A) in the general population?

CEP164 p.Met183Lys (c.548T>A) is rare (popmax 0.103%, sas) (gnomAD).

What do computational predictors say about CEP164 p.Met183Lys (c.548T>A)?

AlphaMissense predicts likely benign (score 0.1126) — an in-silico prediction, not a clinical call.

CEP164 p.Met183Lys

c.548T>A · rs144206271 · VCV573184

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.1126 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.103%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1126	likely benign
REVEL	0.183	benign-leaning
SaProt	LLR -4.94	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 -6.7	GERP -2.9
Regional constraint	o/e 0.97	unconstrained · MANE · 74 kb · p 0.19 · regional, not allelic
Overall
CADD	0.028	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 0.103% South Asian · 85/82,272 alleles

Filtering AF 0.0856% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.079%

Overall 0.0632% 992/1,569,196 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.103%	968
Ashkenazi Jewishnot grpmax-eligible	0.088%	1,137
European (non-Finnish)	0.0698%	1,433
Middle Eastern	0.0518%	1,931
Remaining individualsnot grpmax-eligible	0.0513%	1,950
Finnishnot grpmax-eligible	0.0385%	2,597
African / African-American	0.0151%	6,633
Admixed American	0.00596%	16,771

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: CEP164
Protein: p.Met183Lys
Coding: c.548T>A
MANE Select: NM_014956
dbSNP: rs144206271
Type: single nucleotide variant
Location: chr11:117361989 (GRCh38)
Gene constraint: LOEUF 1.009 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.08 · 4 PDB
Residue 183: the 'interaction with atrip' region

Full CEP164 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: nephronophthisis 15 inherited retinal dystrophy

Similar variants

CEP164 p.Met183Leu Uncertain significance ★ ⚠ same residue
CEP164 p.Met183Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
CEP164 p.Met183Val Conflicting classifications of pathogenicity ★ ⚠ same residue
CEP164 c.1234-2A>T Likely pathogenic ★★ same condition
CEP164 c.1724+1G>A Likely pathogenic ★★ same condition
CEP164 c.1934+1G>A Likely pathogenic ★★ same condition
CEP164 c.2361+1G>A Likely pathogenic ★★ same condition
CEP164 c.2493+1G>A Likely pathogenic ★★ same condition

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/cep164-p-met183lys (accessed [today's date]).

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