Is MFAP5 p.Ser2= (c.6G>A) pathogenic?

MFAP5 p.Ser2= (c.6G>A) is classified Benign/Likely benign in MFAP5 (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-04-01). Rare (popmax 0.472%, nfe); Associated with aortic aneurysm, familial thoracic 9.

What condition is associated with MFAP5 p.Ser2= (c.6G>A)?

MFAP5 p.Ser2= (c.6G>A) is associated with aortic aneurysm, familial thoracic 9 (ClinVar).

How common is MFAP5 p.Ser2= (c.6G>A) in the general population?

MFAP5 p.Ser2= (c.6G>A) is rare (popmax 0.472%, nfe) (gnomAD).

MFAP5 p.Ser2=

Q: How is Familial thoracic aortic aneurysm and aortic dissection inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.6G>A · rs4132450 · VCV388139

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

gnomAD v4.1

Rare

rare (popmax 0.472%, nfe)

Conditions

aortic aneurysm, familial thoracic 9

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.25 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.5	GERP 0.89, phastCons 1
Overall
CADD	15.13	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.472% European (non-Finnish) · 5,569/1,179,870 alleles

Filtering AF 0.462% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.457%

Overall 0.378% 6,103/1,613,416 alleles · rare exomes 5,706/1,461,190 · genomes 397/152,226 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.472%	212
Remaining individualsnot grpmax-eligible	0.328%	305
Finnishnot grpmax-eligible	0.191%	524
Admixed American	0.0983%	1,017
Ashkenazi Jewishnot grpmax-eligible	0.0777%	1,287
African / African-American	0.0747%	1,340
South Asian	0.0715%	1,399
Middle Eastern	0.0685%	1,461

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: MFAP5
Protein: p.Ser2=
Coding: c.6G>A
MANE Select: NM_003480
dbSNP: rs4132450
Type: single nucleotide variant
Location: chr12:8662099 (GRCh38)
Gene constraint: LOEUF 0.975 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.79

Full MFAP5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

aortic aneurysm, familial thoracic 9 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Familial thoracic aortic aneurysm and aortic dissection (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood

Similar variants

MFAP5 p.Ser2Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
MFAP5 p.Ser2Pro Uncertain significance ★ ⚠ same residue
MFAP5 c.247+1G>C Uncertain significance ★★ same condition
MFAP5 p.Asp51Val Uncertain significance ★★ ⚠ same condition
MFAP5 p.His132Leu Uncertain significance ★★ ⚠ same condition
MFAP5 p.Leu139Phe Uncertain significance ★★ ⚠ same condition
MFAP5 p.Leu62Trp Uncertain significance ★★ ⚠ same condition
MFAP5 c.172+5A>G Benign/Likely benign ★★ 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/mfap5-p-ser2 (accessed [today's date]).

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