Is AFF1 p.Ser627Cys (c.1879A>T) pathogenic?

AFF1 p.Ser627Cys (c.1879A>T) is classified Likely benign in AFF1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-04-04). AlphaMissense: likely benign (0.0752); Rare (popmax 0.271%, afr).

How common is AFF1 p.Ser627Cys (c.1879A>T) in the general population?

AFF1 p.Ser627Cys (c.1879A>T) is rare (popmax 0.271%, afr) (gnomAD).

What do computational predictors say about AFF1 p.Ser627Cys (c.1879A>T)?

AlphaMissense predicts likely benign (score 0.0752) — an in-silico prediction, not a clinical call.

AFF1 p.Ser627Cys

c.1879A>T · rs113026065 · VCV786039

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0752 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.271%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0752	likely benign
REVEL	0.081	moderately benign-leaning
SaProt	LLR -8.79	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 -0.086	GERP -4.8
Regional constraint	o/e 1.07	unconstrained · MANE · 84 kb · p 0.031 · regional, not allelic
Overall
CADD	6.75	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S620C vs ClinVar S627C) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.271% African / African-American · 203/74,994 alleles

Filtering AF 0.24% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.228%

Overall 0.0188% 303/1,613,938 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.271%	369
Middle Eastern	0.099%	1,010
Admixed American	0.055%	1,819
Remaining individualsnot grpmax-eligible	0.0528%	1,894
European (non-Finnish)	0.00229%	43,703
South Asian	0.0011%	91,074

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: AFF1
Protein: p.Ser627Cys
Coding: c.1879A>T
MANE Select: NM_001166693
dbSNP: rs113026065
Type: single nucleotide variant
Location: chr4:87114712 (GRCh38)
Gene constraint: LOEUF 0.49 · pLI 0.95 (gnomAD)
Structure: AlphaFold pLDDT 53.06 · 1 PDB
Residue 627: the 'disordered' region

Full AFF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AFF1 c.1191+8C>T Benign/Likely benign ★★ same type
AFF1 p.Ala40= Benign ★★ same type
AFF1 p.Pro393= Benign ★★ same type
AFF1 p.Thr426= Likely benign ★★ same type
AFF1 p.Val711Ile Benign ★★ same type
AFF1 p.Ala1047Val Uncertain significance ★ ⚠ same type
AFF1 p.Ala1103Thr Uncertain significance ★ ⚠ same type
AFF1 p.Ala127Val 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/aff1-p-ser627cys (accessed [today's date]).

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