Is MAVS p.Pro66= (c.198C>T) pathogenic?

MAVS p.Pro66= (c.198C>T) is classified Benign in MAVS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-05-17). Common (popmax 6.65%, afr) — too common for a highly-penetrant pathogenic allele.

MAVS p.Pro66=

Q: How common is MAVS p.Pro66= (c.198C>T) in the general population?

MAVS p.Pro66= (c.198C>T) is common (popmax 6.65%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.198C>T · rs11905658 · VCV782663

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 6.65%, afr) — too common for a highly-penetrant pathogenic allele

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 -20	GERP -3.1
Overall
CADD	0.052	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.65% African / African-American · 4,990/75,038 alleles

Filtering AF 6.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.43%

Overall 0.351% 5,671/1,614,214 alleles · common exomes 2,777/1,461,888 · genomes 2,894/152,326 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.65%	15
Admixed American	0.448%	223
Remaining individualsnot grpmax-eligible	0.446%	224
Middle Eastern	0.379%	264
South Asian	0.0132%	7,590
European (non-Finnish)	0.0083%	12,041

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: MAVS
Protein: p.Pro66=
Coding: c.198C>T
MANE Select: NM_020746
dbSNP: rs11905658
Type: single nucleotide variant
Location: chr20:3857715 (GRCh38)
Gene constraint: LOEUF 0.898 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 56.31 · 11 PDB
Residue 66: the card domain; the 'required for interaction with nlrx1' region

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

Similar variants

MAVS c.292+6C>T Benign ★★ same type
MAVS p.Ala497= Benign ★★ same type
MAVS p.Gly413Ser Benign ★★ same type
MAVS p.Gly491= Likely benign ★★ same type
MAVS p.Ala264Glu Uncertain significance ★ ⚠ same type
MAVS p.Ala356Gly Uncertain significance ★ ⚠ same type
MAVS p.Ala74Val Uncertain significance ★ ⚠ same type
MAVS p.Ala85Thr 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/mavs-p-pro66 (accessed [today's date]).

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