Is DFFB p.Ala131Val (c.392C>T) pathogenic?

DFFB p.Ala131Val (c.392C>T) is classified Uncertain significance in DFFB (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-17). AlphaMissense: likely benign (0.0982); Very rare (popmax 0.00899%, eas).

How common is DFFB p.Ala131Val (c.392C>T) in the general population?

DFFB p.Ala131Val (c.392C>T) is very rare (popmax 0.00899%, eas) (gnomAD).

What do computational predictors say about DFFB p.Ala131Val (c.392C>T)?

AlphaMissense predicts likely benign (score 0.0982) — an in-silico prediction, not a clinical call.

DFFB p.Ala131Val

c.392C>T · rs1041052283 · VCV2209014

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0982 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00899%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0982	likely benign
REVEL	0.043	moderately benign-leaning
SaProt	LLR -6.00	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 -2.8	GERP -3.6
Regional constraint	o/e 0.90	unconstrained · MANE · 26 kb · p 0.042 · regional, not allelic
Overall
CADD	4.929	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00899% East Asian · 4/44,502 alleles

Filtering AF 0.00299% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00181%

Overall 0.00227% 36/1,587,388 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00899%	11,126
Admixed American	0.00341%	29,301
African / African-American	0.00268%	37,291
European (non-Finnish)	0.00241%	41,561

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.Ala131Val
Coding: c.392C>T
MANE Select: NM_004402
dbSNP: rs1041052283
Type: single nucleotide variant
Location: chr1:3865962 (GRCh38)
Gene constraint: LOEUF 1.143 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.60 · 1 PDB

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.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
DFFB p.Arg196Gly 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-ala131val (accessed [today's date]).

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