Is TM4SF20 p.Pro44Ser (c.130C>T) pathogenic?

TM4SF20 p.Pro44Ser (c.130C>T) is classified Uncertain significance in TM4SF20 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-27). AlphaMissense: likely benign (0.1975); Absent from gnomAD v4.1.

How common is TM4SF20 p.Pro44Ser (c.130C>T) in the general population?

TM4SF20 p.Pro44Ser (c.130C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TM4SF20 p.Pro44Ser (c.130C>T)?

AlphaMissense predicts likely benign (score 0.1975) — an in-silico prediction, not a clinical call.

TM4SF20 p.Pro44Ser

c.130C>T · rs2106497649 · VCV1472274

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1975 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1975	likely benign
REVEL	0.084	moderately benign-leaning
SaProt	LLR -5.57	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 5	GERP 0.21, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 16 kb · p 0.41 · regional, not allelic
Overall
CADD	21.3	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TM4SF20
Protein: p.Pro44Ser
Coding: c.130C>T
MANE Select: NM_024795
dbSNP: rs2106497649
Type: single nucleotide variant
Location: chr2:227379139 (GRCh38)
Gene constraint: LOEUF 1.228 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.10

Full TM4SF20 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TM4SF20 c.250-2A>G Uncertain significance ★★ same type
TM4SF20 p.Arg75Ser Uncertain significance ★★ ⚠ same type
TM4SF20 p.Ile93Thr Uncertain significance ★★ ⚠ same type
TM4SF20 p.Ser91Gly Uncertain significance ★★ ⚠ same type
TM4SF20 p.Trp170Ter Uncertain significance ★★ same type
TM4SF20 p.Val221Ile Uncertain significance ★★ ⚠ same type
TM4SF20 c.250-13T>C Likely benign ★★ same type
TM4SF20 p.Ala27Val Benign ★★ 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/tm4sf20-p-pro44ser (accessed [today's date]).

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