Is MFAP1 p.Arg436Gln (c.1307G>A) pathogenic?

MFAP1 p.Arg436Gln (c.1307G>A) is classified Uncertain significance in MFAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-12). AlphaMissense: likely benign (0.3125); Very rare (popmax 0.00539%, afr).

How common is MFAP1 p.Arg436Gln (c.1307G>A) in the general population?

MFAP1 p.Arg436Gln (c.1307G>A) is very rare (popmax 0.00539%, afr) (gnomAD).

What do computational predictors say about MFAP1 p.Arg436Gln (c.1307G>A)?

AlphaMissense predicts likely benign (score 0.3125) — an in-silico prediction, not a clinical call.

MFAP1 p.Arg436Gln

c.1307G>A · rs767759857 · VCV2206073

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3125 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00539%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3125	likely benign
REVEL	0.127	moderately benign-leaning
SaProt	LLR -4.67	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 7.5	GERP -0.076, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 291 bp · p 4.2e-05 · regional, not allelic
Overall
CADD	24.9	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 0.00539% African / African-American · 4/74,248 alleles

Filtering AF 0.00176% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00105%

Overall 0.00145% 23/1,582,272 alleles · very rare exomes 21/1,430,102 · genomes 2/152,170 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00539%	18,562
Admixed American	0.00513%	19,507
East Asian	0.00227%	44,032
Remaining individualsnot grpmax-eligible	0.00164%	60,954
European (non-Finnish)	0.00113%	88,883
South Asian	0.00112%	89,474

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.Arg436Gln
Coding: c.1307G>A
MANE Select: NM_005926
dbSNP: rs767759857
Type: single nucleotide variant
Location: chr15:43805107 (GRCh38)
Gene constraint: LOEUF 0.412 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.84 · 14 PDB

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.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
MFAP1 p.Glu98Gly 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-arg436gln (accessed [today's date]).

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