Is MFAP5 p.Pro148Ser (c.442C>T) pathogenic?

MFAP5 p.Pro148Ser (c.442C>T) is classified Conflicting classifications of pathogenicity in MFAP5 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-24). AlphaMissense: likely benign (0.2982); Low-frequency (popmax 1.77%, mid); Associated with Cardiovascular phenotype.

What condition is associated with MFAP5 p.Pro148Ser (c.442C>T)?

MFAP5 p.Pro148Ser (c.442C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is MFAP5 p.Pro148Ser (c.442C>T) in the general population?

MFAP5 p.Pro148Ser (c.442C>T) is low-frequency (popmax 1.77%, mid) (gnomAD).

What do computational predictors say about MFAP5 p.Pro148Ser (c.442C>T)?

AlphaMissense predicts likely benign (score 0.2982) — an in-silico prediction, not a clinical call.

MFAP5 p.Pro148Ser

c.442C>T · rs148770543 · VCV432223

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.2982 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.77%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.2982	likely benign
REVEL	0.139	moderately benign-leaning
SaProt	LLR -9.65	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 9.8	GERP 1.7, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 14 kb · p 0.45 · regional, not allelic
Overall
CADD	23.8	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 1.77% Middle Eastern · 107/6,058 alleles

Filtering AF 1.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.39%

Overall 0.039% 630/1,613,794 alleles · low-frequency exomes 589/1,461,544 · genomes 41/152,250 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	1.77%	57
Admixed American	0.07%	1,429
Remaining individualsnot grpmax-eligible	0.0688%	1,453
African / African-American	0.036%	2,779
South Asian	0.034%	2,938
European (non-Finnish)	0.0321%	3,113
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,602

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.Pro148Ser
Coding: c.442C>T
MANE Select: NM_003480
dbSNP: rs148770543
Type: single nucleotide variant
Location: chr12:8648171 (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

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MFAP5 c.140-3C>A Uncertain significance ★★ same condition
MFAP5 c.335+4A>G Uncertain significance ★★ same condition
MFAP5 c.336-3C>T Uncertain significance ★★ same condition
MFAP5 p.Arg115His Uncertain significance ★★ same condition
MFAP5 p.Arg126His Uncertain significance ★★ same condition
MFAP5 p.Arg30Gln Uncertain significance ★★ ⚠ same condition
MFAP5 p.Arg93Ser Uncertain significance ★★ ⚠ same condition
MFAP5 p.Arg99Trp 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/mfap5-p-pro148ser (accessed [today's date]).

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