Is AFF3 p.Pro104Leu (c.311C>T) pathogenic?

AFF3 p.Pro104Leu (c.311C>T) is classified Uncertain significance in AFF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-07-10). AlphaMissense: likely benign (0.0962); Absent from gnomAD v4.1.

How common is AFF3 p.Pro104Leu (c.311C>T) in the general population?

AFF3 p.Pro104Leu (c.311C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AFF3 p.Pro104Leu (c.311C>T)?

AlphaMissense predicts likely benign (score 0.0962) — an in-silico prediction, not a clinical call.

AFF3 p.Pro104Leu

c.311C>T · rs2104740337 · VCV1184311

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0962 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0962	likely benign
REVEL	0.461	indeterminate
SaProt	LLR -10.47	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 2,107 bp · p 0.95 · regional, not allelic
Overall
CADD	26.7	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: AFF3
Protein: p.Pro104Leu
Coding: c.311C>T
MANE Select: NM_001386135
dbSNP: rs2104740337
Type: single nucleotide variant
Location: chr2:100007324 (GRCh38)
Gene constraint: LOEUF 0.318 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 52.20

Full AFF3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AFF3 p.Pro104_Val105insGlnThrPro Uncertain significance ★ same residue
AFF3 p.Ala233Thr Pathogenic ★★ ⚠ same type
AFF3 p.Ala233Val Pathogenic/Likely pathogenic ★★ ⚠ same type
AFF3 p.Ile1147Asn Uncertain significance ★★ ⚠ same type
AFF3 p.Leu370Phe Uncertain significance ★★ ⚠ same type
AFF3 p.Pro321Leu Uncertain significance ★★ ⚠ same type
AFF3 p.Ser222Thr Uncertain significance ★★ ⚠ same type
AFF3 p.Thr950Met 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/aff3-p-pro104leu (accessed [today's date]).

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