Is DCBLD2 p.Phe45Ser (c.134T>C) pathogenic?

DCBLD2 p.Phe45Ser (c.134T>C) is classified Likely benign in DCBLD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-28). AlphaMissense: likely benign (0.0568); Ultra-rare (popmax 0.0183%, mid).

How common is DCBLD2 p.Phe45Ser (c.134T>C) in the general population?

DCBLD2 p.Phe45Ser (c.134T>C) is ultra-rare (popmax 0.0183%, mid) (gnomAD).

What do computational predictors say about DCBLD2 p.Phe45Ser (c.134T>C)?

AlphaMissense predicts likely benign (score 0.0568) — an in-silico prediction, not a clinical call.

DCBLD2 p.Phe45Ser

c.134T>C · rs368040324 · VCV2467131

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0568 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0183%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0568	likely benign
REVEL	0.268	benign-leaning
SaProt	LLR -2.99	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 0.3	GERP -2.4, phastCons 0.06
Regional constraint	o/e 1.15	unconstrained · MANE · 76 kb · p 0.018 · regional, not allelic
Overall
CADD	16.97	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 0.0183% Middle Eastern · 1/5,452 alleles

Filtering AF 0.00638% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00478%

Overall 0.00351% 54/1,536,812 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0183%	5,452
African / African-American	0.0123%	8,110
Remaining individualsnot grpmax-eligible	0.01%	9,997
East Asian	0.00489%	20,454
Admixed American	0.00392%	25,480
South Asian	0.00357%	28,006
European (non-Finnish)	0.0027%	36,989

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: DCBLD2
Protein: p.Phe45Ser
Coding: c.134T>C
MANE Select: NM_080927
dbSNP: rs368040324
Type: single nucleotide variant
Location: chr3:98901193 (GRCh38)
Gene constraint: LOEUF 0.808 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.13

Full DCBLD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DCBLD2 p.Lys391= Benign ★★ same type
DCBLD2 p.Ala182Thr Uncertain significance ★ ⚠ same type
DCBLD2 p.Ala24Ser Uncertain significance ★ ⚠ same type
DCBLD2 p.Ala304Glu Uncertain significance ★ ⚠ same type
DCBLD2 p.Ala304Thr Uncertain significance ★ ⚠ same type
DCBLD2 p.Ala304Val Uncertain significance ★ ⚠ same type
DCBLD2 p.Ala341Thr Uncertain significance ★ ⚠ same type
DCBLD2 p.Ala482Asp 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/dcbld2-p-phe45ser (accessed [today's date]).

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