Is MEFV p.Pro188= (c.564C>T) pathogenic?

MEFV p.Pro188= (c.564C>T) is classified Conflicting classifications of pathogenicity in MEFV (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2026-02-02). Rare (popmax 0.101%, sas); Associated with Inborn genetic diseases.

What condition is associated with MEFV p.Pro188= (c.564C>T)?

MEFV p.Pro188= (c.564C>T) is associated with Inborn genetic diseases, familial Mediterranean fever (ClinVar).

How common is MEFV p.Pro188= (c.564C>T) in the general population?

MEFV p.Pro188= (c.564C>T) is rare (popmax 0.101%, sas) (gnomAD).

MEFV p.Pro188=

c.564C>T · rs775755423 · VCV319116

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

rare (popmax 0.101%, sas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6.7	GERP -3.6
Overall
CADD	0.185	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.101% South Asian · 89/88,308 alleles

Filtering AF 0.0838% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0775%

Overall 0.00758% 119/1,569,408 alleles · rare exomes 109/1,417,178 · genomes 10/152,230 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.101%	992
Remaining individualsnot grpmax-eligible	0.00494%	20,239
Admixed American	0.00378%	26,464
East Asian	0.0023%	43,422
European (non-Finnish)	0.00198%	50,488
African / African-American	0.00136%	73,712

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: MEFV
Protein: p.Pro188=
Coding: c.564C>T
MANE Select: NM_000243
dbSNP: rs775755423
Type: single nucleotide variant
Location: chr16:3254504 (GRCh38)
Gene constraint: LOEUF 1.147 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 73.64 · 11 PDB
Residue 188: the 'disordered' region

Full MEFV 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: familial Mediterranean fever

Similar variants

MEFV p.Arg761His Pathogenic/Likely pathogenic ★★ ⚠ same condition
MEFV p.Ser242Arg Pathogenic/Likely pathogenic ★★ same condition
MEFV p.Val726Ala Pathogenic/Likely pathogenic ★★ ⚠ same condition
MEFV c.*845C>T Uncertain significance ★★ same condition
MEFV p.Ala193Thr Uncertain significance ★★ ⚠ same condition
MEFV p.Ala2Gly Uncertain significance ★★ ⚠ same condition
MEFV p.Ala416Thr Uncertain significance ★★ ⚠ same condition
MEFV p.Ala768Gly Uncertain significance ★★ ⚠ 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/mefv-p-pro188 (accessed [today's date]).

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