Is MFAP5 p.Ser28= (c.84T>C) pathogenic?

MFAP5 p.Ser28= (c.84T>C) is classified Likely benign in MFAP5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-15). Very rare (popmax 0.000339%, nfe).

How common is MFAP5 p.Ser28= (c.84T>C) in the general population?

MFAP5 p.Ser28= (c.84T>C) is very rare (popmax 0.000339%, nfe) (gnomAD).

MFAP5 p.Ser28=

c.84T>C · VCV3686531

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.008	strongly benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.38	GERP -2.3, phastCons 0.79
Overall
CADD	4.31	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,179,022 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,612,574 alleles · very rare exomes 4/1,460,700 · genomes 0/151,874 · joint denominator

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.Ser28=
Coding: c.84T>C
MANE Select: NM_003480
Type: single nucleotide variant
Location: chr12:8660873 (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

Similar variants

MFAP5 p.Ser28Gly Uncertain significance ★ ⚠ same residue
MFAP5 c.140-3C>A Uncertain significance ★★ same type
MFAP5 c.217+1G>T Uncertain significance ★★ same type
MFAP5 c.247+1G>C Uncertain significance ★★ same type
MFAP5 c.335+4A>G Uncertain significance ★★ same type
MFAP5 c.336-3C>T Uncertain significance ★★ same type
MFAP5 p.Arg115His Uncertain significance ★★ same type
MFAP5 p.Arg126Cys 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/mfap5-p-ser28 (accessed [today's date]).

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