Is AFF4 p.Ser210Cys (c.629C>G) pathogenic?

AFF4 p.Ser210Cys (c.629C>G) is classified Uncertain significance in AFF4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-20). AlphaMissense: likely benign (0.0877); Ultra-rare (popmax 0.0178%, eas); Associated with Inborn genetic diseases.

What condition is associated with AFF4 p.Ser210Cys (c.629C>G)?

AFF4 p.Ser210Cys (c.629C>G) is associated with Inborn genetic diseases (ClinVar).

How common is AFF4 p.Ser210Cys (c.629C>G) in the general population?

AFF4 p.Ser210Cys (c.629C>G) is ultra-rare (popmax 0.0178%, eas) (gnomAD).

What do computational predictors say about AFF4 p.Ser210Cys (c.629C>G)?

AlphaMissense predicts likely benign (score 0.0877) — an in-silico prediction, not a clinical call.

AFF4 p.Ser210Cys

c.629C>G · VCV3274694

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0877 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0178%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0877	likely benign
REVEL	0.187	benign-leaning
SaProt	LLR -10.28	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 4, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 477 bp · p 0.29 · regional, not allelic
Overall
CADD	27.7	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 0.0178% East Asian · 8/44,896 alleles

Filtering AF 0.00883% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00641%

Overall 0.000991% 16/1,614,036 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0178%	5,612
European (non-Finnish)	0.000678%	147,505

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: AFF4
Protein: p.Ser210Cys
Coding: c.629C>G
MANE Select: NM_014423
Type: single nucleotide variant
Location: chr5:132934436 (GRCh38)
Gene constraint: LOEUF 0.114 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 54.62 · 9 PDB
Residue 210: the 'disordered' region

Full AFF4 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

AFF4 p.Ala27Thr Uncertain significance ★★ ⚠ same condition
AFF4 p.Ala489Thr Uncertain significance ★★ ⚠ same condition
AFF4 p.Arg153His Uncertain significance ★★ ⚠ same condition
AFF4 p.Arg225His Uncertain significance ★★ ⚠ same condition
AFF4 p.Arg3Cys Uncertain significance ★★ ⚠ same condition
AFF4 p.Arg531Gln Uncertain significance ★★ ⚠ same condition
AFF4 p.Arg711Thr Uncertain significance ★★ ⚠ same condition
AFF4 p.Asn762Ser 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/aff4-p-ser210cys (accessed [today's date]).

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