Is DFFB p.Glu50Gly (c.149A>G) pathogenic?

DFFB p.Glu50Gly (c.149A>G) is classified Uncertain significance in DFFB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-09). AlphaMissense: likely benign (0.2925); Rare (popmax 0.141%, sas).

How common is DFFB p.Glu50Gly (c.149A>G) in the general population?

DFFB p.Glu50Gly (c.149A>G) is rare (popmax 0.141%, sas) (gnomAD).

What do computational predictors say about DFFB p.Glu50Gly (c.149A>G)?

AlphaMissense predicts likely benign (score 0.2925) — an in-silico prediction, not a clinical call.

DFFB p.Glu50Gly

c.149A>G · VCV3271674

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2925 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.141%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2925	likely benign
REVEL	0.431	indeterminate
SaProt	LLR -12.45	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 11	GERP 1.5, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 26 kb · p 0.042 · regional, not allelic
Overall
CADD	27.8	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 0.141% South Asian · 128/91,086 alleles

Filtering AF 0.121% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.113%

Overall 0.00849% 137/1,614,170 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.141%	712
Remaining individualsnot grpmax-eligible	0.0048%	20,837
Admixed American	0.00333%	30,015
European (non-Finnish)	0.000339%	295,011

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: DFFB
Protein: p.Glu50Gly
Coding: c.149A>G
MANE Select: NM_004402
Type: single nucleotide variant
Location: chr1:3858752 (GRCh38)
Gene constraint: LOEUF 1.143 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.60 · 1 PDB
Residue 50: the cide-n domain; a β-strand

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

Similar variants

DFFB p.Ala103Thr Uncertain significance ★ ⚠ same type
DFFB p.Ala12Gly Uncertain significance ★ ⚠ same type
DFFB p.Ala131Val Uncertain significance ★ ⚠ same type
DFFB p.Ala132Pro Uncertain significance ★ ⚠ same type
DFFB p.Ala211Thr Uncertain significance ★ ⚠ same type
DFFB p.Arg115Lys Uncertain significance ★ ⚠ same type
DFFB p.Arg165Gln Uncertain significance ★ ⚠ same type
DFFB p.Arg169Lys 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/dffb-p-glu50gly (accessed [today's date]).

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