Is MFAP5 p.Phe89= (c.267T>C) pathogenic?

MFAP5 p.Phe89= (c.267T>C) is classified Likely benign in MFAP5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-28). Very rare (popmax 0.00659%, sas); Associated with Cardiovascular phenotype.

What condition is associated with MFAP5 p.Phe89= (c.267T>C)?

MFAP5 p.Phe89= (c.267T>C) is associated with Cardiovascular phenotype (ClinVar).

How common is MFAP5 p.Phe89= (c.267T>C) in the general population?

MFAP5 p.Phe89= (c.267T>C) is very rare (popmax 0.00659%, sas) (gnomAD).

MFAP5 p.Phe89=

c.267T>C · rs758477431 · VCV1794678

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00659%, sas)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.168	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.23	GERP -3.6, phastCons 0.3
Overall
CADD	1.045	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00659% South Asian · 6/91,082 alleles

Filtering AF 0.00286% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00195%

Overall 0.000682% 11/1,613,920 alleles · very rare exomes 10/1,461,858 · genomes 1/152,062 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00659%	15,180
African / African-American	0.00267%	37,417
European (non-Finnish)	0.000254%	393,340

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.Phe89=
Coding: c.267T>C
MANE Select: NM_003480
dbSNP: rs758477431
Type: single nucleotide variant
Location: chr12:8650570 (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-phe89 (accessed [today's date]).

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