Is SCTR p.Thr108Pro (c.322A>C) pathogenic?

SCTR p.Thr108Pro (c.322A>C) is classified Uncertain significance in SCTR (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-27). AlphaMissense: ambiguous (0.4118); Ultra-rare (popmax 0.0143%, sas).

How common is SCTR p.Thr108Pro (c.322A>C) in the general population?

SCTR p.Thr108Pro (c.322A>C) is ultra-rare (popmax 0.0143%, sas) (gnomAD).

What do computational predictors say about SCTR p.Thr108Pro (c.322A>C)?

AlphaMissense predicts ambiguous (score 0.4118) — an in-silico prediction, not a clinical call.

SCTR p.Thr108Pro

c.322A>C · VCV3316718

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4118 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0143%, sas)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4118	ambiguous
REVEL	0.73	pathogenic-leaning
SaProt	LLR -14.96	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.9, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 84 kb · p 0.62 · regional, not allelic
Overall
CADD	27.3	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 0.0143% South Asian · 13/91,080 alleles

Filtering AF 0.00844% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00661%

Overall 0.00285% 46/1,613,904 alleles · ultra-rare exomes 43/1,461,710 · genomes 3/152,194 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0143%	7,006
East Asian	0.00445%	22,448
European (non-Finnish)	0.00254%	39,330
Remaining individualsnot grpmax-eligible	0.0016%	62,476

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.Thr108Pro
Coding: c.322A>C
MANE Select: NM_002980
Type: single nucleotide variant
Location: chr2:119473536 (GRCh38)
Gene constraint: LOEUF 1.373 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.18 · 3 PDB

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-thr108pro (accessed [today's date]).

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