Is STRC p.Lys232Glu (c.694A>G) pathogenic?

STRC p.Lys232Glu (c.694A>G) is classified Likely benign in STRC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-27). AlphaMissense: likely benign (0.0477); Very rare (popmax 0.00794%, amr); Associated with Inborn genetic diseases.

What condition is associated with STRC p.Lys232Glu (c.694A>G)?

STRC p.Lys232Glu (c.694A>G) is associated with Inborn genetic diseases (ClinVar).

How common is STRC p.Lys232Glu (c.694A>G) in the general population?

STRC p.Lys232Glu (c.694A>G) is very rare (popmax 0.00794%, amr) (gnomAD).

What do computational predictors say about STRC p.Lys232Glu (c.694A>G)?

AlphaMissense predicts likely benign (score 0.0477) — an in-silico prediction, not a clinical call.

STRC p.Lys232Glu

c.694A>G · rs876657585 · VCV227973

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0477 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00794%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0477	likely benign
REVEL	0.162	moderately benign-leaning
SaProt	LLR -4.83	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 0.44	GERP 0.86, phastCons 0.031
Regional constraint	o/e 0.00	constrained · MANE · 7,566 bp · p 1.3e-74 · regional, not allelic
Overall
CADD	7.086	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 0.00794% Admixed American · 4/50,350 alleles

Filtering AF 0.00265% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00155%

Overall 0.001% 13/1,297,246 alleles · very rare exomes 12/1,169,060 · genomes 1/128,186 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00794%	12,587
Remaining individualsnot grpmax-eligible	0.0077%	12,986
European (non-Finnish)	0.000537%	186,329

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.Lys232Glu
Coding: c.694A>G
MANE Select: NM_153700
dbSNP: rs876657585
Type: single nucleotide variant
Location: chr15:43617727 (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-lys232glu (accessed [today's date]).

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