Is AFF2 p.Pro1283Ser (c.3847C>T) pathogenic?

AFF2 p.Pro1283Ser (c.3847C>T) is classified Uncertain significance in AFF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-10-30). AlphaMissense: likely pathogenic (0.6342); Very rare (popmax 0.00772%, nfe).

How common is AFF2 p.Pro1283Ser (c.3847C>T) in the general population?

AFF2 p.Pro1283Ser (c.3847C>T) is very rare (popmax 0.00772%, nfe) (gnomAD).

What do computational predictors say about AFF2 p.Pro1283Ser (c.3847C>T)?

AlphaMissense predicts likely pathogenic (score 0.6342) — an in-silico prediction, not a clinical call.

AFF2 p.Pro1283Ser

c.3847C>T · rs1326755554 · VCV449700

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6342 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00772%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6342	likely pathogenic
REVEL	0.587	indeterminate
SaProt	LLR -6.99	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.52	unconstrained · MANE · 3,863 bp · p 0.00012 · regional, not allelic
Overall
CADD	24.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00772% European (non-Finnish) · 69/893,207 alleles

Filtering AF 0.00621% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00569%

Overall 0.0058% 70/1,206,666 alleles · very rare exomes 68/1,094,743 · genomes 2/111,923 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00772%	12,945
African / African-American	0.00175%	57,039

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: AFF2
Protein: p.Pro1283Ser
Coding: c.3847C>T
MANE Select: NM_002025
dbSNP: rs1326755554
Type: single nucleotide variant
Location: chrX:148991243 (GRCh38)
Structure: AlphaFold pLDDT 49.27

Full AFF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AFF2 p.Pro1283Arg Uncertain significance ★ ⚠ same residue
AFF2 c.3267+5G>C Uncertain significance ★★ same type
AFF2 p.Ala1197Thr Uncertain significance ★★ ⚠ same type
AFF2 p.Ala171Pro Uncertain significance ★★ ⚠ same type
AFF2 p.Arg1238Cys Uncertain significance ★★ ⚠ same type
AFF2 p.Arg1295Cys Uncertain significance ★★ ⚠ same type
AFF2 p.Arg670His Uncertain significance ★★ ⚠ same type
AFF2 p.Asn77Ile 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/aff2-p-pro1283ser (accessed [today's date]).

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