Is MAF p.Thr196Pro (c.586A>C) pathogenic?

MAF p.Thr196Pro (c.586A>C) is classified Uncertain significance in MAF (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-05). AlphaMissense: likely benign (0.0552); Very rare (popmax 0.00633%, amr); Associated with Inborn genetic diseases.

What condition is associated with MAF p.Thr196Pro (c.586A>C)?

MAF p.Thr196Pro (c.586A>C) is associated with Inborn genetic diseases (ClinVar).

How common is MAF p.Thr196Pro (c.586A>C) in the general population?

MAF p.Thr196Pro (c.586A>C) is very rare (popmax 0.00633%, amr) (gnomAD).

What do computational predictors say about MAF p.Thr196Pro (c.586A>C)?

AlphaMissense predicts likely benign (score 0.0552) — an in-silico prediction, not a clinical call.

MAF p.Thr196Pro

c.586A>C · rs2143808215 · VCV2376144

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0552 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00633%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0552	likely benign
REVEL	0.354	indeterminate
SaProt	LLR -5.39	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.1	GERP -2.9, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 679 bp · p 0.14 · regional, not allelic
Overall
CADD	18.7	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 0.00633% Admixed American · 1/15,786 alleles

Overall 0.000204% 2/981,108 alleles · very rare exomes 0/838,232 · genomes 2/142,876 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00633%	15,786
European (non-Finnish)	0.000121%	829,607

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.Thr196Pro
Coding: c.586A>C
MANE Select: NM_005360
dbSNP: rs2143808215
Type: single nucleotide variant
Location: chr16:79599317 (GRCh38)
Gene constraint: LOEUF 0.852 · pLI 0.03 (gnomAD)
Structure: AlphaFold pLDDT 62.21
Residue 196: the 'represses are-mediated transcription' region; the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MAF p.Thr196= Likely benign ★★ same residue
MAF p.Arg306Gly Pathogenic/Likely pathogenic ★★ same condition
MAF p.Ser57Phe Likely pathogenic ★★ same condition
MAF p.His394Leu Uncertain significance ★★ same condition
WWOX p.Ala388Val Uncertain significance ★★ ⚠ same condition
WWOX p.Ala399Thr Uncertain significance ★★ ⚠ same condition
WWOX p.Arg395Trp Uncertain significance ★★ ⚠ same condition
WWOX p.Glu391Gly 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/maf-p-thr196pro (accessed [today's date]).

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