Is MAF p.Pro179Ser (c.535C>T) pathogenic?

MAF p.Pro179Ser (c.535C>T) is classified Uncertain significance in MAF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-23). AlphaMissense: likely benign (0.1183); Ultra-rare (popmax 0.0263%, afr).

How common is MAF p.Pro179Ser (c.535C>T) in the general population?

MAF p.Pro179Ser (c.535C>T) is ultra-rare (popmax 0.0263%, afr) (gnomAD).

What do computational predictors say about MAF p.Pro179Ser (c.535C>T)?

AlphaMissense predicts likely benign (score 0.1183) — an in-silico prediction, not a clinical call.

MAF p.Pro179Ser

c.535C>T · VCV3769468

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1183 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0263%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1183	likely benign
REVEL	0.343	indeterminate
SaProt	LLR -6.46	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.2	GERP 1.7, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 679 bp · p 0.14 · regional, not allelic
Overall
CADD	23.6	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 0.0263% African / African-American · 15/57,056 alleles

Filtering AF 0.0161% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.013%

Overall 0.0015% 15/998,396 alleles · ultra-rare exomes 4/851,922 · genomes 11/146,474 · 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: MAF
Protein: p.Pro179Ser
Coding: c.535C>T
MANE Select: NM_005360
Type: single nucleotide variant
Location: chr16:79599368 (GRCh38)
Gene constraint: LOEUF 0.852 · pLI 0.03 (gnomAD)
Structure: AlphaFold pLDDT 62.21
Residue 179: the 'represses are-mediated transcription' region; the 'disordered' region

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

Similar variants

MAF p.Pro179= Likely benign ★ same residue
MAF p.Ala302Val Pathogenic/Likely pathogenic ★★ same type
MAF p.Arg299Cys Pathogenic/Likely pathogenic ★★ same type
MAF p.Arg306Gly Pathogenic/Likely pathogenic ★★ same type
MAF p.Cys305Phe Likely pathogenic ★★ same type
MAF p.Pro59His Pathogenic/Likely pathogenic ★★ same type
MAF p.Ser54Leu Pathogenic ★★ same type
MAF p.Ser57Phe Likely pathogenic ★★ 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/maf-p-pro179ser (accessed [today's date]).

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