Is STRC p.Val1683Ile (c.5047G>A) pathogenic?

STRC p.Val1683Ile (c.5047G>A) is classified Uncertain significance in STRC (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-03). AlphaMissense: likely benign (0.0566); Ultra-rare (popmax 0.016%, amr); Associated with Inborn genetic diseases.

What condition is associated with STRC p.Val1683Ile (c.5047G>A)?

STRC p.Val1683Ile (c.5047G>A) is associated with Inborn genetic diseases (ClinVar).

How common is STRC p.Val1683Ile (c.5047G>A) in the general population?

STRC p.Val1683Ile (c.5047G>A) is ultra-rare (popmax 0.016%, amr) (gnomAD).

What do computational predictors say about STRC p.Val1683Ile (c.5047G>A)?

AlphaMissense predicts likely benign (score 0.0566) — an in-silico prediction, not a clinical call.

STRC p.Val1683Ile

c.5047G>A · rs754612418 · VCV2396400

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0566 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.016%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0566	likely benign
REVEL	0.087	moderately benign-leaning
SaProt	LLR -3.09	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 3.2	GERP -3, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 649 bp · p 0.42 · regional, not allelic
Overall
CADD	15.79	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 0.016% Admixed American · 8/49,980 alleles

Filtering AF 0.00796% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00575%

Overall 0.00538% 69/1,281,374 alleles · ultra-rare exomes 65/1,135,780 · genomes 4/145,594 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.016%	6,248
European (non-Finnish)	0.00619%	16,166
Ashkenazi Jewishnot grpmax-eligible	0.00372%	26,870
South Asian	0.00255%	39,162
Remaining individualsnot grpmax-eligible	0.00195%	51,354
Finnishnot grpmax-eligible	0.00172%	58,198

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: STRC
Protein: p.Val1683Ile
Coding: c.5047G>A
MANE Select: NM_153700
dbSNP: rs754612418
Type: single nucleotide variant
Location: chr15:43600240 (GRCh38)
Gene constraint: LOEUF 0.713 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.21

Full STRC 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

STRC c.4701+1G>A Pathogenic/Likely pathogenic ★★ same condition
STRC p.Arg1102Gln Uncertain significance ★★ ⚠ same condition
STRC p.Arg1237Trp Uncertain significance ★★ ⚠ same condition
STRC p.Arg1338Gln Uncertain significance ★★ ⚠ same condition
STRC p.Arg56His Uncertain significance ★★ ⚠ same condition
STRC p.Arg832Trp Uncertain significance ★★ same condition
STRC p.Arg92Gln Uncertain significance ★★ ⚠ same condition
STRC p.Cys1464Tyr 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/strc-p-val1683ile (accessed [today's date]).

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