Is SCTR p.Leu345Phe (c.1033C>T) pathogenic?

SCTR p.Leu345Phe (c.1033C>T) is classified Uncertain significance in SCTR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-20). AlphaMissense: likely benign (0.3039); Very rare (popmax 0.00275%, afr).

How common is SCTR p.Leu345Phe (c.1033C>T) in the general population?

SCTR p.Leu345Phe (c.1033C>T) is very rare (popmax 0.00275%, afr) (gnomAD).

What do computational predictors say about SCTR p.Leu345Phe (c.1033C>T)?

AlphaMissense predicts likely benign (score 0.3039) — an in-silico prediction, not a clinical call.

SCTR p.Leu345Phe

c.1033C>T · VCV3951168

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3039 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00275%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.3039	likely benign
REVEL	0.343	indeterminate
SaProt	LLR -10.79	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.2, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 84 kb · p 0.62 · regional, not allelic
Overall
CADD	24.7	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 0.00275% African / African-American · 2/72,650 alleles

Filtering AF 0.000457% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000171%

Overall 0.000192% 3/1,561,688 alleles · very rare exomes 2/1,409,484 · genomes 1/152,204 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00275%	36,325
East Asian	0.0024%	41,636

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: SCTR
Protein: p.Leu345Phe
Coding: c.1033C>T
MANE Select: NM_002980
Type: single nucleotide variant
Location: chr2:119446866 (GRCh38)
Gene constraint: LOEUF 1.373 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.18 · 3 PDB
Residue 345: an α-helix

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

Similar variants

SCTR p.Leu345Val Uncertain significance ★ ⚠ same residue
SCTR c.851+10C>T Benign ★★ same type
SCTR p.Ala292Thr Likely benign ★★ same type
SCTR p.Asp110Asn Benign ★★ same type
SCTR p.Cys208= Benign ★★ same type
SCTR p.Leu190= Benign ★★ same type
SCTR p.Pro415= Benign ★★ same type
SCTR p.Ala245Thr 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/sctr-p-leu345phe (accessed [today's date]).

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