Is DEFB107A p.Val9Phe (c.25G>T) pathogenic?

DEFB107A p.Val9Phe (c.25G>T) is classified Benign in DEFB107A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2017-06-26). AlphaMissense: likely benign (0.0502); Common (popmax 50.2%, eas) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about DEFB107A p.Val9Phe (c.25G>T)?

AlphaMissense predicts likely benign (score 0.0502) — an in-silico prediction, not a clinical call.

DEFB107A p.Val9Phe

Q: How common is DEFB107A p.Val9Phe (c.25G>T) in the general population?

DEFB107A p.Val9Phe (c.25G>T) is common (popmax 50.2%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.25G>T · rs2246582 · VCV768223

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0502 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 50.2%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0502	likely benign
REVEL	0.026	moderately benign-leaning
SaProt	LLR -5.34	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 1.1	GERP -5.2
Regional constraint	o/e 0.00	constrained · MANE · 3,817 bp · p 2e-05 · regional, not allelic
Overall
CADD	4.002	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 50.2% East Asian · 17,239/34,332 alleles

Filtering AF 49.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 49.3%

Overall 46.8% 398,572/851,678 alleles · common

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	51.2%	2
East Asiangrpmax	50.2%	2
African / African-American	49.4%	2
Admixed American	48.7%	2
Remaining individualsnot grpmax-eligible	47%	2
European (non-Finnish)	46.5%	2
Finnishnot grpmax-eligible	45.7%	2
Middle Eastern	45.7%	2
South Asian	45.4%	2
Ashkenazi Jewishnot grpmax-eligible	44.6%	2

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: DEFB107A
Protein: p.Val9Phe
Coding: c.25G>T
MANE Select: NM_001037668
dbSNP: rs2246582
Type: single nucleotide variant
Location: chr8:7815604 (GRCh38)
Structure: AlphaFold pLDDT 83.39

Full DEFB107A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/defb107a-p-val9phe (accessed [today's date]).

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