Is TRIO p.Ser15Phe (c.44C>T) pathogenic?

TRIO p.Ser15Phe (c.44C>T) is classified Conflicting classifications of pathogenicity in TRIO (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2021-10-01). AlphaMissense: likely benign (0.1853); Rare (popmax 0.14%, afr); Associated with Inborn genetic diseases.

What condition is associated with TRIO p.Ser15Phe (c.44C>T)?

TRIO p.Ser15Phe (c.44C>T) is associated with Inborn genetic diseases (ClinVar).

How common is TRIO p.Ser15Phe (c.44C>T) in the general population?

TRIO p.Ser15Phe (c.44C>T) is rare (popmax 0.14%, afr) (gnomAD).

What do computational predictors say about TRIO p.Ser15Phe (c.44C>T)?

AlphaMissense predicts likely benign (score 0.1853) — an in-silico prediction, not a clinical call.

TRIO p.Ser15Phe

c.44C>T · rs1006366530 · VCV1242140

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1853 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.14%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1853	likely benign
REVEL	0.14	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.4	GERP 0.34, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 137 kb · p 0.027 · regional, not allelic
Overall
CADD	23.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.14% African / African-American · 80/57,162 alleles

Filtering AF 0.115% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.106%

Overall 0.00915% 92/1,005,088 alleles · rare exomes 32/858,746 · genomes 60/146,342 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.14%	715
Middle Eastern	0.0963%	1,038
Remaining individualsnot grpmax-eligible	0.0162%	6,184
Admixed American	0.0121%	8,288
European (non-Finnish)	0.000355%	281,600

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: TRIO
Protein: p.Ser15Phe
Coding: c.44C>T
MANE Select: NM_007118
dbSNP: rs1006366530
Type: single nucleotide variant
Location: chr5:14143769 (GRCh38)
Gene constraint: LOEUF 0.217 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TRIO c.2391+1G>A Pathogenic/Likely pathogenic ★★ same condition
TRIO c.6153+1G>A Pathogenic/Likely pathogenic ★★ same condition
TRIO p.Lys1431Met Pathogenic ★★ same condition
TRIO p.Ala1760Val Uncertain significance ★★ ⚠ same condition
TRIO p.Ala2517Glu Uncertain significance ★★ ⚠ same condition
TRIO p.Ala3036Thr Uncertain significance ★★ ⚠ same condition
TRIO p.Ala3044Val Uncertain significance ★★ ⚠ same condition
TRIO p.Arg122Leu Uncertain significance ★★ same condition

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/trio-p-ser15phe (accessed [today's date]).

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