Is SCTR p.Leu312Phe (c.934C>T) pathogenic?

SCTR p.Leu312Phe (c.934C>T) is classified Uncertain significance in SCTR (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-19). AlphaMissense: likely benign (0.1149); Rare (popmax 0.108%, afr).

How common is SCTR p.Leu312Phe (c.934C>T) in the general population?

SCTR p.Leu312Phe (c.934C>T) is rare (popmax 0.108%, afr) (gnomAD).

What do computational predictors say about SCTR p.Leu312Phe (c.934C>T)?

AlphaMissense predicts likely benign (score 0.1149) — an in-silico prediction, not a clinical call.

SCTR p.Leu312Phe

c.934C>T · VCV3438514

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1149 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.108%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1149	likely benign
REVEL	0.067	moderately benign-leaning
SaProt	LLR -8.47	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 7.3	GERP -1.4, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 84 kb · p 0.62 · regional, not allelic
Overall
CADD	21.2	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

Grpmax group 0.108% African / African-American · 80/74,370 alleles

Filtering AF 0.0885% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0815%

Overall 0.00555% 88/1,586,552 alleles · rare exomes 34/1,434,344 · genomes 54/152,208 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.108%	930
Admixed American	0.00501%	19,979
Remaining individualsnot grpmax-eligible	0.00488%	20,501
European (non-Finnish)	0.000173%	577,587

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.Leu312Phe
Coding: c.934C>T
MANE Select: NM_002980
Type: single nucleotide variant
Location: chr2:119448768 (GRCh38)
Gene constraint: LOEUF 1.373 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.18 · 3 PDB
Residue 312: an α-helix

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

Similar variants

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
SCTR p.Ala375Val 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-leu312phe (accessed [today's date]).

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