Is MFAP5 p.Pro23Ser (c.67C>T) pathogenic?

MFAP5 p.Pro23Ser (c.67C>T) is classified Uncertain significance in MFAP5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-18). AlphaMissense: likely benign (0.092); Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with MFAP5 p.Pro23Ser (c.67C>T)?

MFAP5 p.Pro23Ser (c.67C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is MFAP5 p.Pro23Ser (c.67C>T) in the general population?

MFAP5 p.Pro23Ser (c.67C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MFAP5 p.Pro23Ser (c.67C>T)?

AlphaMissense predicts likely benign (score 0.092) — an in-silico prediction, not a clinical call.

MFAP5 p.Pro23Ser

c.67C>T · VCV4054240

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.092 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.092	likely benign
REVEL	0.116	moderately benign-leaning
SaProt	LLR -6.89	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2	GERP -2, phastCons 0.25
Regional constraint	o/e 0.95	unconstrained · MANE · 14 kb · p 0.45 · regional, not allelic
Overall
CADD	8.902	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MFAP5
Protein: p.Pro23Ser
Coding: c.67C>T
MANE Select: NM_003480
Type: single nucleotide variant
Location: chr12:8660890 (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 p.Pro23Ala Uncertain significance ★ ⚠ same residue
MFAP5 p.Pro23Leu Uncertain significance ★ ⚠ same residue
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

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-pro23ser (accessed [today's date]).

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