Is MFAP1 p.Ser94Arg (c.280A>C) pathogenic?

MFAP1 p.Ser94Arg (c.280A>C) is classified Uncertain significance in MFAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-30). AlphaMissense: likely benign (0.2978); Rare (popmax 0.214%, nfe).

How common is MFAP1 p.Ser94Arg (c.280A>C) in the general population?

MFAP1 p.Ser94Arg (c.280A>C) is rare (popmax 0.214%, nfe) (gnomAD).

What do computational predictors say about MFAP1 p.Ser94Arg (c.280A>C)?

AlphaMissense predicts likely benign (score 0.2978) — an in-silico prediction, not a clinical call.

MFAP1 p.Ser94Arg

c.280A>C · rs11556438 · VCV3125644

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2978 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.214%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2978	likely benign
REVEL	0.068	moderately benign-leaning
SaProt	LLR -4.71	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 7.7	GERP 1.8, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 7,531 bp · p 5e-06 · regional, not allelic
Overall
CADD	21.3	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

Grpmax group 0.214% European (non-Finnish) · 2,520/1,180,018 alleles

Filtering AF 0.207% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.204%

Overall 0.161% 2,600/1,613,798 alleles · rare exomes 2,464/1,461,492 · genomes 136/152,306 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.214%	468
Remaining individualsnot grpmax-eligible	0.0768%	1,302
African / African-American	0.0333%	3,001
Finnishnot grpmax-eligible	0.00937%	10,673
Admixed American	0.00167%	60,012

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: MFAP1
Protein: p.Ser94Arg
Coding: c.280A>C
MANE Select: NM_005926
dbSNP: rs11556438
Type: single nucleotide variant
Location: chr15:43817248 (GRCh38)
Gene constraint: LOEUF 0.412 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.84 · 14 PDB
Residue 94: a modified residue (phosphoserine); the 'disordered' region

Full MFAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MFAP1 p.Arg306His Uncertain significance ★ ⚠ same type
MFAP1 p.Arg316Lys Uncertain significance ★ ⚠ same type
MFAP1 p.Arg436Gln Uncertain significance ★ ⚠ same type
MFAP1 p.Arg87Gln Uncertain significance ★ ⚠ same type
MFAP1 p.Gln14His Uncertain significance ★ ⚠ same type
MFAP1 p.Glu163Asp Uncertain significance ★ ⚠ same type
MFAP1 p.Glu318Ala Uncertain significance ★ same type
MFAP1 p.Glu78Asp 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/mfap1-p-ser94arg (accessed [today's date]).

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