Is STRC p.Arg782His (c.2345G>A) pathogenic?

STRC p.Arg782His (c.2345G>A) is classified Uncertain significance in STRC (ClinVar, Single submitter, 1 submitter; last evaluated 2016-12-13). AlphaMissense: likely benign (0.0992); Rare (popmax 0.349%, afr).

How common is STRC p.Arg782His (c.2345G>A) in the general population?

STRC p.Arg782His (c.2345G>A) is rare (popmax 0.349%, afr) (gnomAD).

What do computational predictors say about STRC p.Arg782His (c.2345G>A)?

AlphaMissense predicts likely benign (score 0.0992) — an in-silico prediction, not a clinical call.

STRC p.Arg782His

c.2345G>A · rs1293358821 · VCV499240

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0992 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.349%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0992	likely benign
REVEL	0.141	moderately benign-leaning
SaProt	LLR -7.27	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 0.13	GERP -2.2, phastCons 0.93
Regional constraint	o/e 0.00	constrained · MANE · 7,566 bp · p 1.3e-74 · regional, not allelic
Overall
CADD	18.28	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 0.349% African / African-American · 18/5,154 alleles

Filtering AF 0.226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.186%

Overall 0.0141% 27/191,206 alleles · rare exomes 27/190,640 · genomes 0/566 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.349%	286
Admixed American	0.0289%	3,455
East Asian	0.011%	9,116
Remaining individualsnot grpmax-eligible	0.0104%	9,574
South Asian	0.00295%	33,944
European (non-Finnish)	0.00275%	36,359

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.Arg782His
Coding: c.2345G>A
MANE Select: NM_153700
dbSNP: rs1293358821
Type: single nucleotide variant
Location: chr15:43614022 (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

Similar variants

STRC p.Arg782Cys Uncertain significance ★ same residue
STRC c.4219-1G>A Pathogenic/Likely pathogenic ★★ same type
STRC c.4701+1G>A Pathogenic/Likely pathogenic ★★ same type
STRC p.Arg1073Ter Pathogenic ★★ same type
STRC p.Arg1154Ter Pathogenic/Likely pathogenic ★★ same type
STRC p.Arg1224Ter Pathogenic ★★ same type
STRC p.Arg1338Ter Pathogenic/Likely pathogenic ★★ same type
STRC p.Arg1451Ter Pathogenic/Likely pathogenic ★★ 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/strc-p-arg782his (accessed [today's date]).

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