Is BCAS4 p.Ser130Thr (c.388T>A) pathogenic?

BCAS4 p.Ser130Thr (c.388T>A) is classified Benign in BCAS4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). AlphaMissense: likely benign (0.1028); Low-frequency (popmax 2.88%, afr).

How common is BCAS4 p.Ser130Thr (c.388T>A) in the general population?

BCAS4 p.Ser130Thr (c.388T>A) is low-frequency (popmax 2.88%, afr) (gnomAD).

What do computational predictors say about BCAS4 p.Ser130Thr (c.388T>A)?

AlphaMissense predicts likely benign (score 0.1028) — an in-silico prediction, not a clinical call.

BCAS4 p.Ser130Thr

c.388T>A · rs2145692 · VCV713432

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1028 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.88%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1028	likely benign
REVEL	0.022	moderately benign-leaning
SaProt	LLR -6.96	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 -2.5	GERP -3.3
Regional constraint	o/e 0.94	unconstrained · MANE · 82 kb · p 0.36 · regional, not allelic
Overall
CADD	0.395	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 S160T vs ClinVar S130T) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.88% African / African-American · 2,124/73,766 alleles

Filtering AF 2.78% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.74%

Overall 0.169% 2,684/1,585,184 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.88%	35
Admixed American	0.273%	366
Remaining individualsnot grpmax-eligible	0.248%	404
Middle Eastern	0.203%	492
Ashkenazi Jewishnot grpmax-eligible	0.143%	701
European (non-Finnish)	0.0168%	5,940
South Asian	0.00906%	11,042

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: BCAS4
Protein: p.Ser130Thr
Coding: c.388T>A
MANE Select: NM_198799
dbSNP: rs2145692
Type: single nucleotide variant
Location: chr20:50841889 (GRCh38)
Gene constraint: LOEUF 1.081 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.40

Full BCAS4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BCAS4 p.Ser130Tyr Benign/Likely benign ★★ ⚠ same residue
BCAS4 p.Thr142Met Likely benign ★★ same type
BCAS4 c.-15C>T Uncertain significance ★ ⚠ same type
BCAS4 c.-6C>T Uncertain significance ★ ⚠ same type
BCAS4 p.Ala118Ser Uncertain significance ★ ⚠ same type
BCAS4 p.Ala126Thr Uncertain significance ★ ⚠ same type
BCAS4 p.Ala29Ser Uncertain significance ★ ⚠ same type
BCAS4 p.Ala31Val 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/bcas4-p-ser130thr (accessed [today's date]).

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