Is AFF3 p.Asn905Ser (c.2714A>G) pathogenic?

AFF3 p.Asn905Ser (c.2714A>G) is classified Likely benign in AFF3 (ClinVar, Single submitter, 2 submitters; last evaluated 2026-05-12). AlphaMissense: likely benign (0.0596); Low-frequency (popmax 2.4%, eas).

How common is AFF3 p.Asn905Ser (c.2714A>G) in the general population?

AFF3 p.Asn905Ser (c.2714A>G) is low-frequency (popmax 2.4%, eas) (gnomAD).

What do computational predictors say about AFF3 p.Asn905Ser (c.2714A>G)?

AlphaMissense predicts likely benign (score 0.0596) — an in-silico prediction, not a clinical call.

AFF3 p.Asn905Ser

c.2714A>G · VCV3352035

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0596 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.4%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0596	likely benign
REVEL	0.02	moderately benign-leaning
SaProt	LLR -5.41	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.073	GERP -5.2, phastCons 0.001
Regional constraint	o/e 0.92	unconstrained · MANE · 16 kb · p 0.083 · regional, not allelic
Overall
CADD	0.145	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 2.4% East Asian · 1,078/44,884 alleles

Filtering AF 2.28% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.23%

Overall 0.0784% 1,265/1,614,236 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	2.4%	42
South Asian	0.133%	753
Remaining individualsnot grpmax-eligible	0.0816%	1,226
Middle Eastern	0.0165%	6,062
Admixed American	0.00333%	30,017
African / African-American	0.00133%	75,050
European (non-Finnish)	0.000932%	107,277

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: AFF3
Protein: p.Asn905Ser
Coding: c.2714A>G
MANE Select: NM_001386135
Type: single nucleotide variant
Location: chr2:99582877 (GRCh38)
Gene constraint: LOEUF 0.318 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 52.20
Residue 905: the 'disordered' region

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

Similar variants

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
AFF3 c.1371+7G>A Likely benign ★★ 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-asn905ser (accessed [today's date]).

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