Is SCTR p.Asp43Glu (c.129C>A) pathogenic?

SCTR p.Asp43Glu (c.129C>A) is classified Uncertain significance in SCTR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-04). AlphaMissense: likely benign (0.0671); Ultra-rare (popmax 0.0133%, amr).

How common is SCTR p.Asp43Glu (c.129C>A) in the general population?

SCTR p.Asp43Glu (c.129C>A) is ultra-rare (popmax 0.0133%, amr) (gnomAD).

What do computational predictors say about SCTR p.Asp43Glu (c.129C>A)?

AlphaMissense predicts likely benign (score 0.0671) — an in-silico prediction, not a clinical call.

SCTR p.Asp43Glu

c.129C>A · VCV4160914

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0671 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0671	likely benign
REVEL	0.03	moderately benign-leaning
SaProt	LLR -4.94	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 0.47	GERP 0.55, phastCons 0.99
Regional constraint	o/e 1.02	unconstrained · MANE · 84 kb · p 0.62 · regional, not allelic
Overall
CADD	9.064	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 0.0133% Admixed American · 8/60,004 alleles

Filtering AF 0.00661% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00482%

Overall 0.00173% 28/1,613,926 alleles · ultra-rare exomes 27/1,461,766 · genomes 1/152,160 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0133%	7,501
Remaining individualsnot grpmax-eligible	0.0064%	15,622
African / African-American	0.00134%	74,904
European (non-Finnish)	0.00127%	78,664

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.Asp43Glu
Coding: c.129C>A
MANE Select: NM_002980
Type: single nucleotide variant
Location: chr2:119494492 (GRCh38)
Gene constraint: LOEUF 1.373 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.18 · 3 PDB
Residue 43: 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-asp43glu (accessed [today's date]).

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